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+```{r, child='pkgdown/index.md'}
```
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+License
+ +YEAR: 2019 +COPYRIGHT HOLDER: Gibran Hemani ++ +
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+Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the “Software”), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions:
+The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software.
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+Introduction +
+A data frame of the instruments for an exposure is required. Each +line has the information for one variant for one exposure. The minimum +information required for MR analysis is the following:
+-
+
-
+
SNP- rs ID
+ -
+
beta- The effect size. If the trait is binary then +log(OR) should be used
+ -
+
se- The standard error of the effect size
+ -
+
effect_allele- The allele of the SNP which has the +effect marked inbeta+
+
Other information that is useful for MR can also be provided:
+-
+
-
+
other_allele- The non-effect allele
+ -
+
eaf- The effect allele frequency
+ -
+
Phenotype- The name of the phenotype for which the SNP +has an effect
+
You can also provide the following extra information:
+-
+
-
+
chr- Physical position of variant (chromosome)
+ -
+
position- Physical position of variant (position)
+ -
+
samplesize- Sample size for estimating the effect +size
+ -
+
ncase- Number of cases
+ -
+
ncontrol- Number of controls
+ -
+
pval- The P-value for the SNP’s association with the +exposure
+ -
+
units- The units in which the effects are +presented
+ -
+
gene- The gene or other annotation for the the +SNP
+
+
+Reading in from a file +
+The data can be read in from a text file using the
+read_exposure_data function. The file must have a header
+with column names corresponding to the columns described above.
+
+
+
+Example 1: The default column names are used +
+An example of a text file with the default column names is provided +as part of the package, the first few rows look like this:
+Phenotype SNP beta se effect_allele other_allele eaf pval units gene samplesize
+BMI rs10767664 0.19 0.0306122448979592 A T 0.78 5e-26 kg/m2 BDNF 225238
+BMI rs13078807 0.1 0.0204081632653061 G A 0.2 4e-11 kg/m2 CADM2 221431
+BMI rs1514175 0.07 0.0204081632653061 A G 0.43 8e-14 kg/m2 TNNI3K 207641
+BMI rs1558902 0.39 0.0204081632653061 A T 0.42 5e-120 kg/m2 FTO 222476
+BMI rs10968576 0.11 0.0204081632653061 G A 0.31 3e-13 kg/m2 LRRN6C 247166
+BMI rs2241423 0.13 0.0204081632653061 G A 0.78 1e-18 kg/m2 LBXCOR1 227886The exact path to the file will be different on everyone’s computer, +but it can be located like this:
+
+bmi_file <- system.file("extdata", "bmi.txt", package = "TwoSampleMR")You can read the data in like this:
+
+bmi_exp_dat <- read_exposure_data(bmi_file)
+head(bmi_exp_dat)
+#> SNP beta.exposure se.exposure effect_allele.exposure
+#> 1 rs10767664 0.19 0.03061224 A
+#> 2 rs13078807 0.10 0.02040816 G
+#> 3 rs1514175 0.07 0.02040816 A
+#> 4 rs1558902 0.39 0.02040816 A
+#> 5 rs10968576 0.11 0.02040816 G
+#> 6 rs2241423 0.13 0.02040816 G
+#> other_allele.exposure eaf.exposure pval.exposure units.exposure gene.exposure
+#> 1 T 0.78 5e-26 kg/m2 BDNF
+#> 2 A 0.20 4e-11 kg/m2 CADM2
+#> 3 G 0.43 8e-14 kg/m2 TNNI3K
+#> 4 T 0.42 5e-120 kg/m2 FTO
+#> 5 A 0.31 3e-13 kg/m2 LRRN6C
+#> 6 A 0.78 1e-18 kg/m2 LBXCOR1
+#> samplesize.exposure exposure mr_keep.exposure pval_origin.exposure
+#> 1 225238 BMI TRUE reported
+#> 2 221431 BMI TRUE reported
+#> 3 207641 BMI TRUE reported
+#> 4 222476 BMI TRUE reported
+#> 5 247166 BMI TRUE reported
+#> 6 227886 BMI TRUE reported
+#> units.exposure_dat id.exposure data_source.exposure
+#> 1 kg/m2 ImbABK textfile
+#> 2 kg/m2 ImbABK textfile
+#> 3 kg/m2 ImbABK textfile
+#> 4 kg/m2 ImbABK textfile
+#> 5 kg/m2 ImbABK textfile
+#> 6 kg/m2 ImbABK textfileThe output from this function is a new data frame with standardised +column names:
+-
+
SNP
+exposure
+beta.exposure
+se.exposure
+effect_allele.exposure
+other_allele.exposure
+eaf.exposure
+mr_keep.exposure
+pval.exposure
+pval_origin.exposure
+id.exposure
+data_source.exposure
+units.exposure
+gene.exposure
+samplesize.exposure
+
The function attempts to match the columns to the ones it expects. It +also checks that the data type is as expected.
+If the required data for MR to be performed is not present (SNP name,
+effect size, standard error, effect allele) for a particular SNP, then
+the column mr_keep.exposure will be FALSE.
+
+
+
+
+Example 2: The text file has non-default column names +
+If the text file does not have default column names, this can still +be read in as follows. Here are the first few rows of an example:
+rsid,effect,SE,a1,a2,a1_freq,p-value,Units,Gene,n
+rs10767664,0.19,0.030612245,A,T,0.78,5.00E-26,kg/m2,BDNF,225238
+rs13078807,0.1,0.020408163,G,A,0.2,4.00E-11,kg/m2,CADM2,221431
+rs1514175,0.07,0.020408163,A,G,0.43,8.00E-14,kg/m2,TNNI3K,207641
+rs1558902,0.39,0.020408163,A,T,0.42,5.00E-120,kg/m2,FTO,222476Note that this is a CSV file, with commas separating fields. The file +is located here:
+
+bmi2_file <- system.file("extdata/bmi.csv", package = "TwoSampleMR")To read in this data:
+
+bmi_exp_dat <- read_exposure_data(
+ filename = bmi2_file,
+ sep = ",",
+ snp_col = "rsid",
+ beta_col = "effect",
+ se_col = "SE",
+ effect_allele_col = "a1",
+ other_allele_col = "a2",
+ eaf_col = "a1_freq",
+ pval_col = "p-value",
+ units_col = "Units",
+ gene_col = "Gene",
+ samplesize_col = "n"
+)
+#> No phenotype name specified, defaulting to 'exposure'.
+head(bmi_exp_dat)
+#> SNP beta.exposure se.exposure effect_allele.exposure
+#> 1 rs10767664 0.19 0.03061224 A
+#> 2 rs13078807 0.10 0.02040816 G
+#> 3 rs1514175 0.07 0.02040816 A
+#> 4 rs1558902 0.39 0.02040816 A
+#> 5 rs10968576 0.11 0.02040816 G
+#> 6 rs2241423 0.13 0.02040816 G
+#> other_allele.exposure eaf.exposure pval.exposure units.exposure gene.exposure
+#> 1 T 0.78 5e-26 kg/m2 BDNF
+#> 2 A 0.20 4e-11 kg/m2 CADM2
+#> 3 G 0.43 8e-14 kg/m2 TNNI3K
+#> 4 T 0.42 5e-120 kg/m2 FTO
+#> 5 A 0.31 3e-13 kg/m2 LRRN6C
+#> 6 A 0.78 1e-18 kg/m2 LBXCOR1
+#> samplesize.exposure exposure mr_keep.exposure pval_origin.exposure
+#> 1 225238 exposure TRUE reported
+#> 2 221431 exposure TRUE reported
+#> 3 207641 exposure TRUE reported
+#> 4 222476 exposure TRUE reported
+#> 5 247166 exposure TRUE reported
+#> 6 227886 exposure TRUE reported
+#> units.exposure_dat id.exposure data_source.exposure
+#> 1 kg/m2 Ku3B84 textfile
+#> 2 kg/m2 Ku3B84 textfile
+#> 3 kg/m2 Ku3B84 textfile
+#> 4 kg/m2 Ku3B84 textfile
+#> 5 kg/m2 Ku3B84 textfile
+#> 6 kg/m2 Ku3B84 textfileIf the Phenotype column is not provided (as is the case
+in this example) then it will assume that the phenotype’s name is simply
+“exposure”. This is entered in the exposure column. It can
+be renamed manually:
+bmi_exp_dat$exposure <- "BMI"
+
+
+
+Using an existing data frame +
+If the data already exists as a data frame in R then it can be
+converted into the correct format using the format_data()
+function. For example, here is some randomly created data:
+random_df <- data.frame(
+ SNP = c("rs1", "rs2"),
+ beta = c(1, 2),
+ se = c(1, 2),
+ effect_allele = c("A", "T")
+)
+random_df
+#> SNP beta se effect_allele
+#> 1 rs1 1 1 A
+#> 2 rs2 2 2 TThis can be formatted like so:
+
+random_exp_dat <- format_data(random_df, type = "exposure")
+#> No phenotype name specified, defaulting to 'exposure'.
+#> Warning in format_data(random_df, type = "exposure"): The following columns are not present but are helpful for harmonisation
+#> other_alleleeaf
+#> Inferring p-values
+random_exp_dat
+#> SNP beta.exposure se.exposure effect_allele.exposure exposure
+#> 1 rs1 1 1 A exposure
+#> 2 rs2 2 2 T exposure
+#> mr_keep.exposure pval.exposure pval_origin.exposure id.exposure
+#> 1 TRUE 0.3173105 inferred 4nec1Z
+#> 2 TRUE 0.3173105 inferred 4nec1Z
+#> other_allele.exposure eaf.exposure
+#> 1 NA NA
+#> 2 NA NA
+
+
+Obtaining instruments from existing catalogues +
+A number of sources of instruments have already been curated and are
+available for use. They are provided as data objects in the
+MRInstruments package. To install:
+remotes::install_github("MRCIEU/MRInstruments")This package contains a number of data.frames, each of which is a +repository of SNP-trait associations. How to access the data frames is +detailed below:
+
+
+
+
+GWAS catalog +
+The NHGRI-EBI GWAS catalog contains a catalog of significant +associations obtained from GWASs. This version of the data is filtered +and harmonised to contain associations that have the required data to +perform MR, to ensure that the units used to report effect sizes from a +particular study are all the same, and other data cleaning +operations.
+To use the GWAS catalog:
+
+library(MRInstruments)
+data(gwas_catalog)
+head(gwas_catalog)
+#> Phenotype_simple
+#> 1 Eosinophil percentage of white cells
+#> 2 Eosinophil counts
+#> 3 Medication use (agents acting on the renin-angiotensin system)
+#> 4 Post bronchodilator FEV1
+#> 5 DNA methylation variation (age effect)
+#> 6 Ankylosing spondylitis
+#> MAPPED_TRAIT_EFO
+#> 1 eosinophil percentage of leukocytes
+#> 2 eosinophil count
+#> 3 Agents acting on the renin-angiotensin system use measurement
+#> 4 forced expiratory volume, response to bronchodilator
+#> 5 DNA methylation
+#> 6 ankylosing spondylitis
+#> MAPPED_TRAIT_EFO_URI
+#> 1 http://www.ebi.ac.uk/efo/EFO_0007991
+#> 2 http://www.ebi.ac.uk/efo/EFO_0004842
+#> 3 http://www.ebi.ac.uk/efo/EFO_0009931
+#> 4 http://www.ebi.ac.uk/efo/EFO_0004314, http://purl.obolibrary.org/obo/GO_0097366
+#> 5 http://purl.obolibrary.org/obo/GO_0006306
+#> 6 http://www.ebi.ac.uk/efo/EFO_0003898
+#> Initial_sample_description
+#> 1 172,378 European ancestry individuals
+#> 2 172,275 European ancestry individuals
+#> 3 62,752 European ancestry cases, 174,778 European ancestry controls
+#> 4 10,094 European ancestry current and former smoker individuals, 3,260 African American current and former smoker individuals, 178 current and former smoker individuals
+#> 5 Up to 954 individuals
+#> 6 921 Turkish ancestry cases, 907 Turkish ancestry controls, 422 Iranian ancestry cases, 754 Iranian ancestry controls
+#> Replication_sample_description STUDY.ACCESSION
+#> 1 <NA> GCST004600
+#> 2 <NA> GCST004606
+#> 3 <NA> GCST007930
+#> 4 <NA> GCST003262
+#> 5 <NA> GCST006660
+#> 6 <NA> GCST007844
+#> Phenotype Phenotype_info
+#> 1 Eosinophil percentage of white cells
+#> 2 Eosinophil counts
+#> 3 Medication use (agents acting on the renin-angiotensin system)
+#> 4 Post bronchodilator FEV1
+#> 5 DNA methylation variation (age effect)
+#> 6 Ankylosing spondylitis
+#> PubmedID Author Year SNP chr bp_ens_GRCh38 Region gene
+#> 1 27863252 Astle WJ 2016 rs1000005 21 33060745 21q22.11 AP000282.2
+#> 2 27863252 Astle WJ 2016 rs1000005 21 33060745 21q22.11 AP000282.2
+#> 3 31015401 Wu Y 2019 rs1000010 3 11562645 3p25.3 VGLL4
+#> 4 26634245 Lutz SM 2015 rs10000225 4 144312789 4q31.21 Intergenic
+#> 5 30348214 Zhang Q 2018 rs10000513 4 160334994 4q32.1 NR
+#> 6 30946743 Li Z 2019 rs10000518 4 11502867 4p15.33 HS3ST1
+#> Gene_ens effect_allele other_allele beta se pval
+#> 1 AP000282.2,LINC00945 C G -0.02652552 0.003826531 2e-13
+#> 2 AP000282.2,LINC00945 C G -0.02481715 0.003571429 7e-12
+#> 3 G A -0.03724189 0.006377551 6e-09
+#> 4 Intergenic A T -0.04400000 0.009420188 3e-06
+#> 5 NR <NA> <NA> NA NA 4e-08
+#> 6 G A 0.73396926 NA 6e-06
+#> units eaf date_added_to_MRBASE
+#> 1 unit decrease 0.589400 2019-08-29
+#> 2 unit decrease 0.589400 2019-08-29
+#> 3 unit decrease 0.351806 2019-08-29
+#> 4 NR unit decrease 0.350000 2019-08-29
+#> 5 <NA> NA 2019-08-29
+#> 6 <NA> NA 2019-08-29For example, to obtain instruments for body mass index using the +Speliotes et al 2010 study:
+
+bmi_gwas <-
+ subset(gwas_catalog,
+ grepl("Speliotes", Author) &
+ Phenotype == "Body mass index")
+bmi_exp_dat <- format_data(bmi_gwas)
+
+
+
+Metabolites +
+Independent top hits from GWASs on 121 metabolites in whole blood are
+stored in the metab_qtls data object. Use
+?metab_qtls to get more information.
+data(metab_qtls)
+head(metab_qtls)
+#> phenotype chromosome position SNP effect_allele other_allele eaf
+#> 1 AcAce 8 9181395 rs2169387 G A 0.870251
+#> 2 AcAce 11 116648917 rs964184 C G 0.857715
+#> 3 Ace 6 12042473 rs6933521 C T 0.120256
+#> 4 Ala 2 27730940 rs1260326 C T 0.638817
+#> 5 Ala 2 65220910 rs2160387 C T 0.403170
+#> 6 Ala 12 47201814 rs4554975 G A 0.644059
+#> beta se pval n_studies n
+#> 1 0.085630 0.015451 3.61e-08 11 19257
+#> 2 -0.096027 0.014624 6.71e-11 11 19261
+#> 3 -0.091667 0.015885 8.10e-09 14 24742
+#> 4 -0.104582 0.009940 7.40e-26 13 22569
+#> 5 -0.071001 0.009603 1.49e-13 14 24793
+#> 6 -0.069135 0.009598 6.12e-13 14 24792For example, to obtain instruments for Alanine:
+
+ala_exp_dat <- format_metab_qtls(subset(metab_qtls, phenotype == "Ala"))
+
+
+
+Proteins +
+Independent top hits from GWASs on 47 protein levels in whole blood
+are stored in the proteomic_qtls data object. Use
+?proteomic_qtls to get more information.
+data(proteomic_qtls)
+head(proteomic_qtls)
+#> analyte chr position SNP gene location annotation other_allele
+#> 1 CFHR1 1 196698945 rs12144939 CFH cis missense T
+#> 2 IL6r 1 154425456 rs12126142 IL6R cis missense A
+#> 3 ApoA4 11 116677723 rs1263167 APOA4 cis intergenic G
+#> 4 SELE 9 136149399 rs507666 ABO trans intronic A
+#> 5 FetuinA 3 186335941 rs2070633 AHSG cis missense T
+#> 6 ACE 17 61566031 rs4343 ACE cis synonymous A
+#> effect_allele eaf maf pval beta se
+#> 1 G 0.643 0.357 8.99e-143 -1.108 0.04355258
+#> 2 G 0.608 0.392 1.81e-106 0.850 0.03878364
+#> 3 A 0.803 0.197 2.64e-54 -0.919 0.05922332
+#> 4 G 0.809 0.191 1.01e-52 -0.882 0.05771545
+#> 5 C 0.676 0.324 2.88e-44 -0.629 0.04506925
+#> 6 G 0.508 0.492 6.66e-44 0.493 0.03547679For example, to obtain instruments for the ApoH protein:
+
+apoh_exp_dat <-
+ format_proteomic_qtls(subset(proteomic_qtls, analyte == "ApoH"))
+
+
+
+Gene expression levels +
+Independent top hits from GWASs on 32432 gene identifiers and in 44
+tissues are available from the GTEX study in gtex_eqtl. Use
+?gtex_eqtl to get more information.
+data(gtex_eqtl)
+head(gtex_eqtl)
+#> tissue gene_name gene_start SNP snp_position
+#> 1 Adipose Subcutaneous RP4-669L17.10 1:317720 rs2519065 1:787151
+#> 2 Adipose Subcutaneous RP11-206L10.1 1:661611 rs11804171 1:723819
+#> 3 Adipose Subcutaneous RP11-206L10.3 1:677193 rs149110718 1:759227
+#> 4 Adipose Subcutaneous RP11-206L10.2 1:700306 rs148649543 1:752796
+#> 5 Adipose Subcutaneous RP11-206L10.9 1:714150 rs12184279 1:717485
+#> 6 Adipose Subcutaneous RP11-206L10.8 1:736259 rs10454454 1:754954
+#> effect_allele other_allele beta se pval n
+#> 1 A G 0.551788 0.0747180 2.14627e-12 298
+#> 2 A T -0.917475 0.1150060 4.99967e-14 298
+#> 3 T C 0.807571 0.1776530 8.44694e-06 298
+#> 4 T C 0.745393 0.0958531 1.82660e-13 298
+#> 5 A C 1.927250 0.2247390 9.55098e-16 298
+#> 6 A G 1.000400 0.1787470 5.61079e-08 298For example, to obtain instruments for the IRAK1BP1 gene expression +levels in subcutaneous adipose tissue:
+
+irak1bp1_exp_dat <-
+ format_gtex_eqtl(subset(
+ gtex_eqtl,
+ gene_name == "IRAK1BP1" & tissue == "Adipose Subcutaneous"
+ ))
+#> Warning in format_data(gtex_eqtl_subset, type = type, phenotype_col = type, : The following columns are not present but are helpful for harmonisation
+#> eaf
+#> Inferring p-values
+
+
+
+DNA methylation levels +
+Independent top hits from GWASs on 0 DNA methylation levels in whole
+blood across 5 time points are available from the ARIES study in
+aries_mqtl. Use ?aries_mqtl to get more
+information.
+data(aries_mqtl)
+head(aries_mqtl)
+#> SNP timepoint cpg beta pval se snp_chr
+#> 1 esv2656832 1 cg21826606 0.3459 1.60408e-26 0.03265336 1
+#> 2 esv2658098 1 cg22681495 -0.6263 1.55765e-66 0.03643240 15
+#> 3 esv2660043 1 cg24276624 -0.5772 3.16370e-26 0.05481823 11
+#> 4 esv2660043 1 cg11157765 -0.5423 1.33928e-22 0.05583777 11
+#> 5 esv2660673 1 cg05832925 -0.5919 2.88011e-50 0.03982467 11
+#> 6 esv2660769 1 cg05859533 -0.6224 1.49085e-58 0.03868158 16
+#> snp_pos effect_allele other_allele eaf sex age units
+#> 1 25591901 I R 0.3974 mixed Birth SD units
+#> 2 86057007 D R 0.2076 mixed Birth SD units
+#> 3 69982552 D R 0.1450 mixed Birth SD units
+#> 4 69982552 D R 0.1450 mixed Birth SD units
+#> 5 74024905 D R 0.1671 mixed Birth SD units
+#> 6 57725395 D R 0.2136 mixed Birth SD units
+#> island_location cpg_chr cpg_pos gene gene_location cis_trans
+#> 1 N_Shore 1 25593055 cis
+#> 2 15 86058755 AKAP13 Body cis
+#> 3 11 69982941 ANO1 Body cis
+#> 4 11 69982996 ANO1 Body cis
+#> 5 S_Shelf 11 74026371 cis
+#> 6 16 57727230 CCDC135 TSS1500 cisFor example, to obtain instruments for cg25212131 CpG DNA methylation +levels in at birth:
+
+cg25212131_exp_dat <-
+ format_aries_mqtl(subset(aries_mqtl, cpg == "cg25212131" &
+ age == "Birth"))
+
+
+
+
+
+
+IEU OpenGWAS database +
+The IEU OpenGWAS database contains the entire summary statistics for +thousands of GWASs. You can browse them here: https://gwas.mrcieu.ac.uk/
+You can use this database to define the instruments for a particular +exposure. You can also use this database to obtain the effects for +constructing polygenic risk scores using different p-value +thresholds.
+You can check the status of the API:
+
+ieugwasr::api_status()To obtain a list and details about the available GWASs do the +following:
+
+ao <- available_outcomes()
+head(ao)For information about authentication see https://mrcieu.github.io/ieugwasr/articles/guide.html#authentication.
+The available_outcomes() function returns a table of all
+the available studies in the database. Each study has a unique ID. e.g.,
+You might obtain
+head(subset(ao, select = c(trait, id)))
+#> trait id
+#> 1 Schizophrenia ieu-b-5103
+#> 2 Schizophrenia ieu-b-5102
+#> 3 Schizophrenia ieu-b-5101
+#> 4 Schizophrenia ieu-b-5100
+#> 5 Schizophrenia ieu-b-5099
+#> 6 Schizophrenia ieu-b-5098To extract instruments for a particular trait using a particular +study, for example to obtain SNPs for body mass index using the Locke et +al. 2015 GIANT study, you specify the study ID as follows:
+
+bmi2014_exp_dat <- extract_instruments(outcomes = 'ieu-a-2')
+str(bmi2014_exp_dat)
+#> 'data.frame': 79 obs. of 15 variables:
+#> $ pval.exposure : num 2.18e-08 4.57e-11 5.06e-14 5.45e-10 1.88e-28 ...
+#> $ samplesize.exposure : num 339152 339065 313621 338768 338123 ...
+#> $ chr.exposure : chr "1" "1" "1" "1" ...
+#> $ se.exposure : num 0.003 0.0031 0.0087 0.0029 0.003 0.0037 0.0031 0.003 0.0038 0.003 ...
+#> $ beta.exposure : num -0.0168 0.0201 0.0659 0.0181 0.0331 0.0497 -0.0227 0.0221 0.0209 0.0175 ...
+#> $ pos.exposure : int 47684677 78048331 110082886 201784287 72837239 177889480 49589847 96924097 164567689 181550962 ...
+#> $ id.exposure : chr "ieu-a-2" "ieu-a-2" "ieu-a-2" "ieu-a-2" ...
+#> $ SNP : chr "rs977747" "rs17381664" "rs7550711" "rs2820292" ...
+#> $ effect_allele.exposure: chr "G" "C" "T" "C" ...
+#> $ other_allele.exposure : chr "T" "T" "C" "A" ...
+#> $ eaf.exposure : num 0.5333 0.425 0.0339 0.5083 0.6083 ...
+#> $ exposure : chr "Body mass index || id:ieu-a-2" "Body mass index || id:ieu-a-2" "Body mass index || id:ieu-a-2" "Body mass index || id:ieu-a-2" ...
+#> $ mr_keep.exposure : logi TRUE TRUE TRUE TRUE TRUE TRUE ...
+#> $ pval_origin.exposure : chr "reported" "reported" "reported" "reported" ...
+#> $ data_source.exposure : chr "igd" "igd" "igd" "igd" ...This returns a set of LD clumped SNPs that are GWAS significant for +BMI. You can specify various parameters for this function:
+-
+
-
+
p1= P-value threshold for keeping a SNP
+ -
+
clump= Whether or not to return independent SNPs only +(default isTRUE)
+ -
+
r2= The maximum LD R-square allowed between returned +SNPs
+ -
+
kb= The distance in which to search for LD R-square +values
+
By changing changing the p1 parameter it is possible to
+obtain SNP effects for constructing polygenic risk scores.
+
+
+
+ Clumping +
+For standard two sample MR it is important to ensure that the +instruments for the exposure are independent. Once instruments have been +identified for an exposure variable, the IEU OpenGWAS database can be +used to perform clumping.
+You can provide a list of SNP IDs, the SNPs will be extracted from +1000 genomes data, LD calculated between them, and amongst those SNPs +that have LD R-square above the specified threshold only the SNP with +the lowest P-value will be retained. To do this, use the following +command:
+
+bmi_exp_dat <- clump_data(bmi2014_exp_dat)
+str(bmi_exp_dat)
+#> 'data.frame': 30 obs. of 16 variables:
+#> $ SNP : chr "rs10767664" "rs13078807" "rs1514175" "rs1558902" ...
+#> $ beta.exposure : num 0.19 0.1 0.07 0.39 0.11 0.13 0.06 0.09 0.13 0.06 ...
+#> $ se.exposure : num 0.0306 0.0204 0.0204 0.0204 0.0204 ...
+#> $ effect_allele.exposure: chr "A" "G" "A" "A" ...
+#> $ other_allele.exposure : chr "T" "A" "G" "T" ...
+#> $ eaf.exposure : num 0.78 0.2 0.43 0.42 0.31 0.78 0.41 0.24 0.21 0.21 ...
+#> $ pval.exposure : num 5e-26 4e-11 8e-14 5e-120 3e-13 ...
+#> $ units.exposure : chr "kg/m2" "kg/m2" "kg/m2" "kg/m2" ...
+#> $ gene.exposure : chr "BDNF" "CADM2" "TNNI3K" "FTO" ...
+#> $ samplesize.exposure : int 225238 221431 207641 222476 247166 227886 209051 218439 209849 220081 ...
+#> $ exposure : chr "BMI" "BMI" "BMI" "BMI" ...
+#> $ mr_keep.exposure : logi TRUE TRUE TRUE TRUE TRUE TRUE ...
+#> $ pval_origin.exposure : chr "reported" "reported" "reported" "reported" ...
+#> $ units.exposure_dat : chr "kg/m2" "kg/m2" "kg/m2" "kg/m2" ...
+#> $ id.exposure : chr "FXhiAH" "FXhiAH" "FXhiAH" "FXhiAH" ...
+#> $ data_source.exposure : chr "textfile" "textfile" "textfile" "textfile" ...The clump_data() function takes any data frame that has
+been formatted to be an exposure data type of data frame. Note that for
+the instruments in the MRInstruments package the SNPs are already LD
+clumped.
Note: The LD reference panel only includes SNPs (no +INDELs). There are five super-populations from which LD can be +calculated, by default European samples are used. Only SNPs with MAF +> 0.01 within-population are available.
+NOTE: If a variant is dropped from your unclumped +data it could be because it is absent from the reference panel. For more +flexibility, including using your own LD reference data, see here: https://mrcieu.github.io/ieugwasr/
+
+
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+
+
+
+
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+
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+ 
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+
+
+
+Major changes to the IEU GWAS resources for 2020
+ + + Source:vignettes/gwas2020.Rmd
+ gwas2020.RmdThis document details changes and new features specifically relating +to the TwoSampleMR R package and the GWAS database behind it.
+
+
+What has changed +
+
+
+Dataset IDs +
+We have made a new system for naming datasets, and all datasets are
+organised into data batches. Either new datasets are uploaded one at a
+time in which case they are added to the ieu-a data batch,
+or there is a bulk upload in which case a new batch is created. For
+example, ukb-a is a bulk upload of the first round of the
+Neale lab UKBiobank GWAS, and ukb-b is the IEU GWAS
+analysis of the UKBiobank data. In most cases, a dataset is then
+numbered arbitrarily within the batch. For example, the Locke et al 2014
+BMI analysis was previously known as 2, and it is now known
+as ieu-a-2.
There is backward compatibility built into the R packages that access +the data, so if you use an ‘old’ ID, it will automatically translate +that to the new one. But it will give you a warning, and we urge you to +update your scripts to reflect this change.
+
+
+Authentication +
+Previously you would automatically be asked to authenticate any query +to the database, through google. Now, we are making authentication +voluntary - something that you do at the start of a session only if you +need access to specific private datasets on the database. For the vast +majority of use cases this is not required.
+Another change is that the R package that managed the authentication +has updated, and the file tokens generated are slightly different. For +full information on how to deal with this, see here: https://mrcieu.github.io/ieugwasr/articles/guide.html#authentication
+
+
+UKBiobank data has been curated +
+We conducted a large GWAS analysis using a pipeline that +systematically analysed every PHESANT phenotype +in UK Biobank. There were previously ~20k traits with complete GWAS +data, but a majority of these were binary traits based on very few +numbers of cases. We have now filtered out unreliable datasets, there +are 2514 traits remaining, with any binary traits removed that had fewer +than 1000 cases. Another issue is the combination of small numbers of +cases and allele frequency - here minor allele count (MAC) for a +particular association could be very small which would lead to high +false positives when using Bolt-LMM. The remaining traits have been +filtered to only retain associations where the MAC > 90.
+Document detailing this investigation here: https://htmlpreview.github.io/?https://raw.githubusercontent.com/MRCIEU/ukbb-gwas-analysis/master/docs/ldsc_clumped_analysis.html?token=AAOV6TBQXEXEPT7SUXXLWMC6DWP3O
+
+
+All data is now harmonised +
+Previously the data were QC’d to remove malformed results and then +deposited as we found them. We are now also pre-harmonising all the +data. This means that all alleles are coded on the forward strand, and +the non-effect allele is always aligned to the human genome reference +sequence B37 (so the effect allele is the non-reference allele). This +does mean that sometimes variants have been removed if they did not map +to the human genome, and for most datasets the effect allele has been +switched for approximately half of all sites. When an effect allele +changes we do of course switch the sign of the effect size, so it should +not impact any MR results.
+
+
+LD reference panel is now harmonised +
+We have updated the LD reference panel to be harmonised against human +genome build 37, and as a consequence a few variants have been lost from +the version that was previously used.
+
+
+
+
+Instrument lists are up-to-date +
+Previously we were pre-clumping the tophits and storing them in the +MRInstruments R package, and there was often a delay in updating the +MRInstruments R package after new datasets were uploaded to the +database. We have moved away from this model. Everything dataset is +pre-clumped, but that is stored in the database. If you request default +clumping values when extracting the tophits of a dataset, it will still +be fast but it is retrieving the data from the server, and not from the +MRInstruments package. You can continue to use the MRInstruments package +for GWAS hits from e.g. GTEx or the EBI GWAS catalog.
+
+
+What is new +
+
+
+Browse available datasets online +
+We have a new home for the GWAS summary data: https://gwas.mrcieu.ac.uk/.
+
+
+
+Chromosome and position +
+All variants have been mapped to chromosome and position
+(hg19/build37). You can query based on chromosome position coordinates.
+This means either a list of <chr:pos> values, or a
+list of <chr:pos1-pos2> ranges.
+
+Multi-allelic variants are retained +
+Previously we were excluding these, but they are now retained. Be +warned that if you extract a variant that has multiple alleles then you +may get more than one row for that variant.
+
+
+More data +
+Automated download from the EBI repository, and an automated upload +system and batch data processing system means that more data can be +added faster to keep the database current.
+
+
+Error messages are more informative +
+Previously if a query to the database failed it didn’t give a reason, +hopefully there is more clarity regarding what is happening now. You can +also check the status of the server here: https://api.opengwas.io/api/
+
+
+Easier programmatic access to the database +
+We are trying to make it as flexible as possible to access the data. +The TwoSampleMR R package was previously the only programmatic way to +access the data, now we have the following options:
+-
+
- +ieugwasr R package: +All the TwoSampleMR functions that access the data are done by calling +this package now. It is a simple wrapper around the API that controls +access to the database. +
- +ieugwaspy python +package: Similar functionality to ieugwasr (Under +construction). +
- +API: You can use the API +directly, e.g. for building your own services or applications. +
+
+Local LD operations +
+It is now possible to perform clumping, or create LD matrices, using +your own local LD reference dataset. You can download the one that we +have been using here: https://github.com/mrcieu/gwasglue#reference-datasets, +or create your own plink format dataset e.g. with larger samples or for +different ancestries. See the LD clumping functions in the ieugwasr package for more +details.
+
+
+Access the data directly +
+Previously the data was only accessible through the database. Now the +data can be downloaded in “GWAS VCF” format from here https://gwas.mrcieu.ac.uk/. (IEU members can access all +the data on RDSF or bluecrystal4 directly). This means that if you want +to perform very large or numerous operations, you can do it on HPC or +locally in a more performant manner by using the data files directly. +Please see the gwasvcf R +package on how to work with these data.
+
+
+Connect the data to different analytical tools +
+Either the data in the database, or the GWAS VCF files, can be +queried and the results translated into the formats for a bunch of +different R packages for MR, colocalisation, fine mapping, etc. Have a +look at the gwasglue R +package, to see what is available and how to do this. It’s still +under construction, but feel free to try it, make suggestions, and +contribute code.
+
+
+Key links +
+-
+
- The IEU GWAS database: https://gwas.mrcieu.ac.uk + +
- API to the IEU GWAS database: https://api.opengwas.io/api/ + +
- ieugwasr package, for R access to the API: https://mrcieu.github.io/ieugwasr/ + +
- ieugwaspy package, for python access to the API: https://github.com/MRCIEU/ieugwaspy/ (Under +construction) +
- gwasvcf package, R interface to GWAS VCF files: https://mrcieu.github.io/gwasvcf/ + +
- pygwasvcf package, python interface to GWAS VCF files: https://github.com/mrcieu/pygwasvcf (Under +construction) +
- gwasglue package, linking GWAS data to various analytical methods: +https://mrcieu.github.io/gwasglue/ (Functional, under +construction) +
- gwas2vcf online tool, allowing users to create GWAS VCF files from +summary data: https://github.com/MRCIEU/gwas2vcf + +
+
+How to request new data +
+We have setup a github issues page here: https://github.com/MRCIEU/opengwas-requests/issues
+Please visit here to make a log of new data requests, or to +contribute new data.
+
+
+
+
+ Backwards compatibility +
+To install the new version of TwoSampleMR, perform as normal:
+
+install.packages("remotes")
+remotes::install_github("MRCIEU/TwoSampleMR")To update the package just run the
+remotes::install_github("MRCIEU/TwoSampleMR") command
+again.
We recommend using this new version going forwards but for a limited +time we are enabling backwards compatibility, in case you are in the +middle of analysis or need to reproduce old analysis. In order to use +the legacy version of the package and the database, install using:
+
+install.packages("remotes")
+remotes::install_github("MRCIEU/TwoSampleMR@0.4.26")
+
+
+
+
+
+
+
+
+
+
+
+
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+
+Introduction +
+The exposure data and outcome data are now obtained, e.g.:
+
+bmi_exp_dat <- extract_instruments(outcomes = 'ieu-a-2')
+chd_out_dat <- extract_outcome_data(snps = bmi_exp_dat$SNP, outcomes = 'ieu-a-7')but it is important to harmonise the effects. This means that the +effect of a SNP on the exposure and the effect of that SNP on the +outcome must each correspond to the same allele.
+Note: The IEU GWAS database contains data that is +already harmonised, meaning that the non-effect allele is aligned to the +human genome reference sequence (build 37). It’s still recommended to +harmonise, but in principle everything should be on the forward strand +and effect alleles always relating to the same allele. Some +discrepancies could arise if there are multi-allelic variants that are +represented as different bi-allelic variants in different studies.
+To harmonise the exposure and outcome data, do the following:
+
+dat <- harmonise_data(
+ exposure_dat = bmi_exp_dat,
+ outcome_dat = chd_out_dat
+)
+#> Harmonising Body mass index || id:ieu-a-2 (ieu-a-2) and Coronary heart disease || id:ieu-a-7 (ieu-a-7)This creates a new data frame that has the exposure data and outcome +data combined.
+If there were 3 exposure traits and 3 outcome traits then there will +be 9 sets of harmonisations being performed - harmonising the SNP +effects of exposure trait 1 against outcome trait 1; exposure trait 1 +against outcome trait 2; and so on.
+
+
+Dealing with strand issues +
+Recent GWASs typically present the effects of a SNP in reference to +the allele on the forward strand. But as reference panels are updated +the forward strand sometimes changes, and GWASs from a few years ago +aren’t guaranteed to be using forward strand conventions.
+Some examples are shown below:
+
+
+Correct, unambigious +
+exposure effect = 0.5
+effect allele = A
+other allele = G
+
+outcome effect = 0.05
+effect allele = A
+other allele = GHere the effect allele on the exposure and the outcome is the +same
+
+
+Incorrect reference, unambigious +
+exposure effect = 0.5
+effect allele = A
+other allele = G
+
+outcome effect = -0.05
+effect allele = C
+other allele = THere the outcome GWAS is presenting the effect for the alternate +allele on the reverse strand. We need to flip the outcome effect to 0.05 +to correspond to the same allele as the exposure GWAS on the forward +strand.
+
+
+Ambiguous +
+exposure effect = 0.5
+effect allele = A
+other allele = G
+
+outcome effect = -0.05
+effect allele = A
+other allele = CHere the alleles do not correspond for the same SNP, so this SNP will +be discarded from the analysis.
+
+
+Palindromic SNP, inferrable +
+exposure effect = 0.5
+effect allele = A
+other allele = T
+effect allele frequency = 0.11
+
+outcome effect = -0.05
+effect allele = A
+other allele = T
+effect allele frequency = 0.91Here the alleles correspond, but it is a palindromic SNP, such that +the alleles on the forward strand are the same as on the reverse strand +(A/T on forward is T/A on the reverse). However, the allele frequency of +the effect allele gives us information - if the outcome effect allele +(A) were on the forward strand we would expect it to have a low allele +frequency, but given it has a high frequency (0.91) we infer that the +outcome GWAS is presenting the effect on the reverse strand for the +alternative allele. We would flip the effect to 0.05 for the outcome +GWAS.
+
+
+Palindromic SNP, not inferrable +
+exposure effect = 0.5
+effect allele = A
+other allele = T
+effect allele frequency = 0.50
+
+outcome effect = -0.05
+effect allele = A
+other allele = T
+effect allele frequency = 0.50This is similar to the above, except the allele frequency no longer +gives us information about the strand. We would discard this SNP. This +is done for any palindromic SNPs that have minor allele frequency above +0.42.
+
+
+Options +
+There are three options to harmonising the data.
+-
+
- Assume all alleles are presented on the forward strand +
- Try to infer the forward strand alleles using allele frequency +information +
- Correct the strand for non-palindromic SNPs, but drop all +palindromic SNPs +
By default, the harmonise_data function uses option 2,
+but this can be modified using the action argument,
+e.g. harmonise_data(exposure_dat, outcome_dat, action = 3).
+
+
+
+
+
+ Drop duplicate exposure-outcome summary sets +
+After data harmonisation, users may find that their dataset contains +duplicate exposure-outcome summary sets. This can arise, for example, +when a GWAS consortium has released multiple results from separate GWAS +analyses for the same trait. For example, there are multiple GWAS +summary datasets for body mass index and coronary heart disease:
+
+ao <- available_outcomes()
+ao[ao$trait == "Body mass index", c("trait", "id", "pmid", "author", "sample_size", "nsnp")]
+#> trait id pmid author
+#> 3958 Body mass index ebi-a-GCST90103751 35051171 Wong HS
+#> 4015 Body mass index ebi-a-GCST90095039 35399580 Fern<U+00E1>ndez-Rhodes L
+#> 4020 Body mass index ebi-a-GCST90095034 35399580 Fern<U+00E1>ndez-Rhodes L
+#> 6032 Body mass index ebi-a-GCST90029007 29892013 Loh PR
+#> 6821 Body mass index ebi-a-GCST90025994 34226706 Barton AR
+#> 7045 Body mass index ebi-a-GCST90018947 34594039 Sakaue S
+#> 7259 Body mass index ebi-a-GCST90018727 34594039 Sakaue S
+#> 10738 Body mass index ieu-a-94 23754948 Randall JC
+#> 12717 Body mass index ieu-a-2 25673413 Locke AE
+#> 14254 Body mass index ieu-a-95 23754948 Randall JC
+#> 16676 Body mass index ieu-a-974 25673413 Locke AE
+#> 19343 Body mass index bbj-a-3 28892062 Ishigaki K
+#> 26475 Body mass index ebi-a-GCST006368 30108127 Hoffmann TJ
+#> 28065 Body mass index ieu-b-4815 NA Howe LJ
+#> 28419 Body mass index bbj-a-2 28892062 Ishigaki K
+#> 32371 Body mass index ieu-b-4816 NA Howe LJ
+#> 33869 Body mass index ieu-a-785 25673413 Locke AE
+#> 39217 Body mass index ebi-a-GCST002783 25673413 Locke AE
+#> 40065 Body mass index bbj-a-1 28892062 Ishigaki K
+#> 43262 Body mass index ebi-a-GCST004904 28892062 Akiyama M
+#> 43743 Body mass index ebi-a-GCST006802 26961502 Wood AR
+#> 47894 Body mass index ieu-a-835 25673413 Locke AE
+#> 48917 Body mass index ebi-a-GCST008025 31217584 Wojcik GL
+#> 49208 Body mass index ieu-a-1089 26961502 Wood
+#> sample_size nsnp
+#> 3958 21930 6370138
+#> 4015 330793 2401077
+#> 4020 56161 8764141
+#> 6032 532396 11973091
+#> 6821 457756 4238669
+#> 7045 359983 19066885
+#> 7259 163835 12502877
+#> 10738 60586 2736876
+#> 12717 339224 2555511
+#> 14254 73137 2736876
+#> 16676 171977 2494613
+#> 19343 72390 6108953
+#> 26475 315347 27854527
+#> 28065 51852 NA
+#> 28419 85894 6108953
+#> 32371 99998 7191606
+#> 33869 152893 2477659
+#> 39217 236781 2529499
+#> 40065 158284 5961600
+#> 43262 158284 5952516
+#> 43743 119688 8580466
+#> 47894 322154 2554668
+#> 48917 21955 34343880
+#> 49208 120286 8654252
+ao[ao$trait == "Coronary heart disease", c("trait", "id", "pmid", "author", "ncase", "ncontrol", "nsnp")]
+#> trait id pmid author ncase
+#> 14897 Coronary heart disease ieu-a-7 26343387 Nikpay 60801
+#> 23614 Coronary heart disease ieu-a-9 23202125 Deloukas 63746
+#> 27414 Coronary heart disease ebi-a-GCST000998 21378990 Schunkert H 22233
+#> 38602 Coronary heart disease ieu-a-8 21378990 Schunkert H 22233
+#> 45294 Coronary heart disease ieu-a-6 21378988 Peden 15420
+#> ncontrol nsnp
+#> 14897 123504 9455779
+#> 23614 130681 79129
+#> 27414 64762 2415020
+#> 38602 64762 2420361
+#> 45294 15062 540233There are therefore multiple potential combinations of body mass +index and coronary heart disease, which would likely lead to duplicate +MR analyses. We recommend that users prune their datasets so that only +the exposure-outcome combination with the highested expected power is +retained. This can be done by selecting the exposure-outcome summary set +with the largest sample size for the outcome, using the power_prune +function:
+
+dat <- power_prune(dat, method = 1, dist.outcome = "binary")This drops the duplicate exposure-outcome sets with the smaller +outcome sample size (number of cases for binary outcomes). Remaining +duplicates are then dropped on the basis of the exposure sample size. +However, if there are a large number of SNPs available to instrument an +exposure, the outcome GWAS with the better SNP coverage may provide +better power than the outcome GWAS with the larger sample size. This can +occur, for example, if the larger outcome GWAS has used a targeted +genotyping array. In such instances, it may be better to prune studies +on the basis of instrument strength (i.e. variation in exposure +explained by the instrumental SNPs) as well as sample size. This can be +done by setting the method argument to 2:
+
+dat <- power_prune(dat, method = 2, dist.outcome = "binary")This procedure drops duplicate exposure-outcome sets on the basis of +instrument strength and sample size, and assumes that the SNP-exposure +effects correspond to a continuous trait with a normal distribution +(i.e. exposure should not be binary). The SNP-outcome effects can +correspond to either a binary or continuous trait (default behaviour is +to assume a binary distribution). If the exposure is binary then method +1 should be used.
+
+
+
+
+
+
+
+
+
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+ Articles
+
+
+
+
+ Guide
+The following pages provide detailed illustrations of the TwoSampleMR package.
- Introduction +
- +
- Exposure data +
- +
- Outcome data +
- +
- Harmonise data +
- +
- Perform MR +
- +
- Major changes to the IEU GWAS resources for 2020 +
- +
+
+
+
+
+
+
+
+
+
+
+
+
diff --git a/docs/articles/outcome.html b/docs/articles/outcome.html
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+
+Background +
+Two sample Mendelian randomisation (2SMR) is a method to estimate the +causal effect of an exposure on an outcome using only summary statistics +from genome wide association studies (GWAS). Though conceptually +straightforward, there are a number of steps that are required to +perform the analysis properly, and they can be cumbersome. The +TwoSampleMR package aims to make this easy by combining three important +components
+-
+
- data management and harmonisation +
- the statistical routines to estimate the causal effects +
- connection to a large repository of the actual GWAS summary +statistics needed to perform the analyses. +
The general principles (G. Davey Smith and +Ebrahim 2003; George Davey Smith and Hemani 2014), and +statistical methods (Pierce and Burgess 2013; +Bowden, Davey Smith, and Burgess 2015) can be found elsewhere, +here we will just outline how to use the R package.
+This package uses the ieugwasr package to +connect to the database of thousands of complete GWAS summary data.
++
+
+
+
+Installation +
+To install directly from the GitHub repository do the following:
+
+library(remotes)
+install_github("MRCIEU/TwoSampleMR")If you don’t have the remotes package install it from
+CRAN using install.packages("remotes").
+
+
+
+Overview +
+The workflow for performing MR is as follows:
+-
+
- Select instruments for the exposure (perform LD clumping if +necessary) +
- Extract the instruments from the IEU GWAS database for the outcomes +of interest +
- Harmonise the effect sizes for the instruments on the exposures and +the outcomes to be each for the same reference allele +
- Perform MR analysis, sensitivity analyses, create plots, compile +reports +
A diagrammatic overview is shown here:
+
A basic analysis, e.g. the causal effect of body mass index on +coronary heart disease, looks like this:
+
+library(TwoSampleMR)
+
+# List available GWASs
+ao <- available_outcomes()
+
+# Get instruments
+exposure_dat <- extract_instruments("ieu-a-2")
+
+# Get effects of instruments on outcome
+outcome_dat <- extract_outcome_data(snps=exposure_dat$SNP, outcomes = "ieu-a-7")
+
+# Harmonise the exposure and outcome data
+dat <- harmonise_data(exposure_dat, outcome_dat)
+
+# Perform MR
+res <- mr(dat)Each step is documented on other pages in the documentation.
+
+
+Authentication +
+The statistical methods in TwoSampleMR can be used on any data, but +there are a number of functions that connect to the OpenGWAS database +for data extraction. These OpenGWAS data access functions require +authentication.
+Authentication is changing The main differences are +that:
+-
+
- Authentication is required for most queries to OpenGWAS for everyone +(i.e. no more anonymous usage) +
- We are no longer using Google Oauth2. This has been replaced by a +simple API key system. +
Detailed information is given here: https://mrcieu.github.io/ieugwasr/articles/guide.html#authentication.
+
+
+ References +
+
+
+
+Bowden, Jack, George Davey Smith, and Stephen Burgess. 2015.
+“Mendelian randomization with invalid
+instruments: effect estimation and bias detection through Egger
+regression.” International Journal of
+Epidemiology 44 (2): 512–25. https://doi.org/10.1093/ije/dyv080.
+
+
+Davey Smith, G., and S. Ebrahim. 2003. “’Mendelian randomization’: can genetic epidemiology
+contribute to understanding environmental determinants of
+disease?” International Journal of Epidemiology
+32 (1): 1–22. https://doi.org/10.1093/ije/dyg070.
+
+
+Davey Smith, George, and Gibran Hemani. 2014. “Mendelian randomization: genetic anchors for causal
+inference in epidemiological studies.” Human Molecular
+Genetics 23 (R1): R89–98. https://doi.org/10.1093/hmg/ddu328.
+
+
+Pierce, Brandon L, and Stephen Burgess. 2013. “Efficient design for Mendelian randomization studies:
+subsample and 2-sample instrumental variable estimators.”
+American Journal of Epidemiology 178 (7): 1177–84. https://doi.org/10.1093/aje/kwt084.
+
+
+
+
+
+
+
+
+
+
+
+
+
+
diff --git a/docs/articles/perform_mr.html b/docs/articles/perform_mr.html
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+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+Once instruments for the exposure trait have been specified, those +variants need to be extracted from the outcome trait.
+
+
+
+
+Available studies in IEU GWAS database +
+The IEU GWAS database (IGD) contains complete GWAS summary statistics +from a large number of studies. You can browse them here:
+ +To obtain details about the available GWASs programmatically do the +following:
+
+ao <- available_outcomes()
+head(ao)
+#> id trait ncase group_name year author consortium
+#> 1 ieu-b-5103 Schizophrenia 1234 public 2022 Trubetskoy V PGC
+#> 2 ieu-b-5102 Schizophrenia 52017 public 2022 Trubetskoy V PGC
+#> 3 ieu-b-5101 Schizophrenia 12305 public 2022 Trubetskoy V PGC
+#> 4 ieu-b-5100 Schizophrenia 64322 public 2022 Trubetskoy V PGC
+#> 5 ieu-b-5099 Schizophrenia 76755 public 2022 Trubetskoy V PGC
+#> 6 ieu-b-5098 Schizophrenia 5998 public 2022 Trubetskoy V PGC
+#> sex pmid population unit
+#> 1 Males and Females 35396580 Hispanic or Latin American logOR
+#> 2 Males and Females 35396580 European logOR
+#> 3 Males and Females 35396580 East Asian logOR
+#> 4 Males and Females 35396580 Mixed logOR
+#> 5 Males and Females 35396580 Mixed logOR
+#> 6 Males and Females 35396580 African American or Afro-Caribbean logOR
+#> sample_size build ncontrol category subcategory ontology
+#> 1 4324 HG19/GRCh37 3090 Disease NA MONDO:0005090
+#> 2 127906 HG19/GRCh37 75889 Disease NA MONDO:0005090
+#> 3 27363 HG19/GRCh37 15058 Disease NA MONDO:0005090
+#> 4 155269 HG19/GRCh37 90947 Disease NA MONDO:0005090
+#> 5 320404 HG19/GRCh37 243649 Disease NA MONDO:0005090
+#> 6 9824 HG19/GRCh37 3826 Disease NA MONDO:0005090
+#> note mr
+#> 1 <NA> NA
+#> 2 <NA> NA
+#> 3 <NA> NA
+#> 4 Core - East Asian and European meta analysis NA
+#> 5 Primary - meta analysis of Eur, East Asian, African American and Latino NA
+#> 6 <NA> NA
+#> nsnp doi coverage study_design priority sd
+#> 1 NA <NA> <NA> <NA> NA NA
+#> 2 NA <NA> <NA> <NA> NA NA
+#> 3 NA <NA> <NA> <NA> NA NA
+#> 4 NA <NA> <NA> <NA> NA NA
+#> 5 NA <NA> <NA> <NA> NA NA
+#> 6 NA <NA> <NA> <NA> NA NAFor information about authentication see https://mrcieu.github.io/ieugwasr/articles/guide.html#authentication.
+The available_outcomes function returns a table of all
+the available studies in the database. Each study has a unique ID.
+e.g.
+
+
+
+
+
+
+Extracting particular SNPs from particular studies +
+If we want to perform MR of BMI against coronary heart disease, we +need to identify the SNPs that influence the BMI, and then extract those +SNPs from a GWAS on coronary heart disease.
+Let’s get the Locke et al 2014 instruments for BMI as an example:
+
+bmi_exp_dat <- extract_instruments(outcomes = 'ieu-a-2')
+head(bmi_exp_dat)
+#> pval.exposure samplesize.exposure chr.exposure se.exposure beta.exposure
+#> 1 2.18198e-08 339152 1 0.0030 -0.0168
+#> 2 4.56773e-11 339065 1 0.0031 0.0201
+#> 3 5.05941e-14 313621 1 0.0087 0.0659
+#> 4 5.45205e-10 338768 1 0.0029 0.0181
+#> 5 1.88018e-28 338123 1 0.0030 0.0331
+#> 6 2.28718e-40 339078 1 0.0037 0.0497
+#> pos.exposure id.exposure SNP effect_allele.exposure
+#> 1 47684677 ieu-a-2 rs977747 G
+#> 2 78048331 ieu-a-2 rs17381664 C
+#> 3 110082886 ieu-a-2 rs7550711 T
+#> 4 201784287 ieu-a-2 rs2820292 C
+#> 5 72837239 ieu-a-2 rs7531118 C
+#> 6 177889480 ieu-a-2 rs543874 G
+#> other_allele.exposure eaf.exposure exposure
+#> 1 T 0.5333 Body mass index || id:ieu-a-2
+#> 2 T 0.4250 Body mass index || id:ieu-a-2
+#> 3 C 0.0339 Body mass index || id:ieu-a-2
+#> 4 A 0.5083 Body mass index || id:ieu-a-2
+#> 5 T 0.6083 Body mass index || id:ieu-a-2
+#> 6 A 0.2667 Body mass index || id:ieu-a-2
+#> mr_keep.exposure pval_origin.exposure data_source.exposure
+#> 1 TRUE reported igd
+#> 2 TRUE reported igd
+#> 3 TRUE reported igd
+#> 4 TRUE reported igd
+#> 5 TRUE reported igd
+#> 6 TRUE reported igdWe now need to find a suitable GWAS for coronary heart disease. We +can search the available studies:
+
+ao[grepl("heart disease", ao$trait), ]
+#> id
+#> 7958 finn-b-I9_CHD
+#> 10829 ukb-b-3983
+#> 12268 ukb-e-I25_AFR
+#> 14221 ukb-b-2205
+#> 14897 ieu-a-7
+#> 15028 finn-b-I9_SECONDRIGHT_EXNONE
+#> 16883 ukb-b-7436
+#> 18046 ukb-a-534
+#> 18048 ukb-e-I25_CSA
+#> 20207 finn-b-I9_OTHHEART
+#> 22249 finn-b-I9_VHD_EXNONE
+#> 22725 finn-b-I9_PULMHEART
+#> 23614 ieu-a-9
+#> 24603 finn-b-FG_OTHHEART
+#> 27414 ebi-a-GCST000998
+#> 33264 finn-b-FG_PULMHEART
+#> 35220 ukb-d-I9_CHD
+#> 35231 finn-b-I9_OTHILLHEART
+#> 36931 ukb-b-8184
+#> 37302 finn-b-I9_OTHILLHEART_EXNONE
+#> 37894 ukb-b-1668
+#> 38319 finn-b-I9_IHD
+#> 38448 finn-b-I9_RHEUFEV
+#> 38602 ieu-a-8
+#> 41994 finn-b-I9_ISCHHEART
+#> 42095 ukb-d-I9_IHD
+#> 42882 finn-b-I9_SECONDRIGHT
+#> 43747 ukb-d-I9_CHD_NOREV
+#> 45294 ieu-a-6
+#> 46126 finn-b-I9_VHD
+#> 46689 ukb-b-16606
+#> trait
+#> 7958 Major coronary heart disease event
+#> 10829 Diagnoses - main ICD10: I25.9 Chronic ischaemic heart disease, unspecified
+#> 12268 I25 Chronic ischaemic heart disease
+#> 14221 Diagnoses - secondary ICD10: Z82.4 Family history of ischaemic heart disease and other diseases of the circulatory system
+#> 14897 Coronary heart disease
+#> 15028 Secondary right heart disease (no controls excluded)
+#> 16883 Diagnoses - secondary ICD10: I25.1 Atherosclerotic heart disease
+#> 18046 Diagnoses - main ICD10: I25 Chronic ischaemic heart disease
+#> 18048 I25 Chronic ischaemic heart disease
+#> 20207 Other heart diseases (I9_OTHHEART)
+#> 22249 Valvular heart disease including rheumatic fever (no controls excluded)
+#> 22725 Pulmonary heart disease, diseases of pulmonary circulation
+#> 23614 Coronary heart disease
+#> 24603 Other heart diseases (FG_OTHHEART)
+#> 27414 Coronary heart disease
+#> 33264 Pulmonary heart disease
+#> 35220 Major coronary heart disease event
+#> 35231 Other or ill-defined heart diseases
+#> 36931 Diagnoses - secondary ICD10: I25.9 Chronic ischaemic heart disease, unspecified
+#> 37302 Other or ill-defined heart diseases (no controls excluded)
+#> 37894 Diagnoses - main ICD10: I25.1 Atherosclerotic heart disease
+#> 38319 Ischaemic heart disease, wide definition
+#> 38448 Rheumatic fever incl heart disease
+#> 38602 Coronary heart disease
+#> 41994 Ischemic heart diseases
+#> 42095 Ischaemic heart disease, wide definition
+#> 42882 Secondary right heart disease
+#> 43747 Major coronary heart disease event excluding revascularizations
+#> 45294 Coronary heart disease
+#> 46126 Valvular heart disease including rheumatic fever
+#> 46689 Diagnoses - secondary ICD10: I25.8 Other forms of chronic ischaemic heart disease
+#> ncase group_name year author consortium sex
+#> 7958 21012 public 2021 NA NA Males and Females
+#> 10829 1195 public 2018 Ben Elsworth MRC-IEU Males and Females
+#> 12268 302 public 2020 Pan-UKB team NA Males and Females
+#> 14221 9330 public 2018 Ben Elsworth MRC-IEU Males and Females
+#> 14897 60801 public 2015 Nikpay CARDIoGRAMplusC4D Males and Females
+#> 15028 428 public 2021 NA NA Males and Females
+#> 16883 5771 public 2018 Ben Elsworth MRC-IEU Males and Females
+#> 18046 8755 public 2017 Neale Neale Lab Males and Females
+#> 18048 1205 public 2020 Pan-UKB team NA Males and Females
+#> 20207 62081 public 2021 NA NA Males and Females
+#> 22249 38209 public 2021 NA NA Males and Females
+#> 22725 4564 public 2021 NA NA Males and Females
+#> 23614 63746 public 2013 Deloukas CARDIoGRAMplusC4D Males and Females
+#> 24603 58173 public 2021 NA NA Males and Females
+#> 27414 22233 public 2011 Schunkert H NA NA
+#> 33264 4185 public 2021 NA NA Males and Females
+#> 35220 10157 public 2018 Neale lab NA Males and Females
+#> 35231 713 public 2021 NA NA Males and Females
+#> 36931 5861 public 2018 Ben Elsworth MRC-IEU Males and Females
+#> 37302 713 public 2021 NA NA Males and Females
+#> 37894 12171 public 2018 Ben Elsworth MRC-IEU Males and Females
+#> 38319 31640 public 2021 NA NA Males and Females
+#> 38448 573 public 2021 NA NA Males and Females
+#> 38602 22233 public 2011 Schunkert H CARDIoGRAM Males and Females
+#> 41994 30952 public 2021 NA NA Males and Females
+#> 42095 20857 public 2018 Neale lab NA Males and Females
+#> 42882 428 public 2021 NA NA Males and Females
+#> 43747 10157 public 2018 Neale lab NA Males and Females
+#> 45294 15420 public 2011 Peden C4D Males and Females
+#> 46126 38209 public 2021 NA NA Males and Females
+#> 46689 5738 public 2018 Ben Elsworth MRC-IEU Males and Females
+#> pmid population unit sample_size
+#> 7958 NA European NA NA
+#> 10829 NA European SD 463010
+#> 12268 NA African American or Afro-Caribbean NA 6636
+#> 14221 NA European SD 463010
+#> 14897 26343387 Mixed log odds 184305
+#> 15028 NA European NA NA
+#> 16883 NA European SD 463010
+#> 18046 NA European SD 337199
+#> 18048 NA South Asian NA 8876
+#> 20207 NA European NA NA
+#> 22249 NA European NA NA
+#> 22725 NA European NA NA
+#> 23614 23202125 Mixed log odds 194427
+#> 24603 NA European NA NA
+#> 27414 21378990 European logOR 86995
+#> 33264 NA European NA NA
+#> 35220 NA European NA 361194
+#> 35231 NA European NA NA
+#> 36931 NA European SD 463010
+#> 37302 NA European NA NA
+#> 37894 NA European SD 463010
+#> 38319 NA European NA NA
+#> 38448 NA European NA NA
+#> 38602 21378990 European log odds 86995
+#> 41994 NA European NA NA
+#> 42095 NA European NA 361194
+#> 42882 NA European NA NA
+#> 43747 NA European NA 361194
+#> 45294 21378988 Mixed log odds 30482
+#> 46126 NA European NA NA
+#> 46689 NA European SD 463010
+#> build ncontrol category subcategory ontology
+#> 7958 HG19/GRCh37 197780 Binary NA NA
+#> 10829 HG19/GRCh37 461815 Binary NA NA
+#> 12268 HG19/GRCh37 6334 Binary NA NA
+#> 14221 HG19/GRCh37 453680 Binary NA NA
+#> 14897 HG19/GRCh37 123504 Disease Cardiovascular NA
+#> 15028 HG19/GRCh37 218364 Binary NA NA
+#> 16883 HG19/GRCh37 457239 Binary NA NA
+#> 18046 HG19/GRCh37 328444 NA NA NA
+#> 18048 HG19/GRCh37 7671 Binary NA NA
+#> 20207 HG19/GRCh37 156711 Binary NA NA
+#> 22249 HG19/GRCh37 180583 Binary NA NA
+#> 22725 HG19/GRCh37 214228 Binary NA NA
+#> 23614 HG19/GRCh37 130681 Disease Cardiovascular NA
+#> 24603 HG19/GRCh37 160619 Binary NA NA
+#> 27414 HG19/GRCh37 64762 NA NA NA
+#> 33264 HG19/GRCh37 214607 Binary NA NA
+#> 35220 HG19/GRCh37 351037 Binary NA NA
+#> 35231 HG19/GRCh37 156711 Binary NA NA
+#> 36931 HG19/GRCh37 457149 Binary NA NA
+#> 37302 HG19/GRCh37 218079 Binary NA NA
+#> 37894 HG19/GRCh37 450839 Binary NA NA
+#> 38319 HG19/GRCh37 187152 Binary NA NA
+#> 38448 HG19/GRCh37 218219 Binary NA NA
+#> 38602 HG19/GRCh37 64762 Disease Cardiovascular NA
+#> 41994 HG19/GRCh37 187840 Binary NA NA
+#> 42095 HG19/GRCh37 340337 Binary NA NA
+#> 42882 HG19/GRCh37 214228 Binary NA NA
+#> 43747 HG19/GRCh37 351037 Binary NA NA
+#> 45294 HG19/GRCh37 15062 Disease Cardiovascular NA
+#> 46126 HG19/GRCh37 156711 Binary NA NA
+#> 46689 HG19/GRCh37 457272 Binary NA NA
+#> note
+#> 7958 I9_CHD
+#> 10829 41202#I259: Output from GWAS pipeline using Phesant derived variables from UKBiobank
+#> 12268 NA
+#> 14221 41204#Z824: Output from GWAS pipeline using Phesant derived variables from UKBiobank
+#> 14897 <NA>
+#> 15028 I9_SECONDRIGHT_EXNONE
+#> 16883 41204#I251: Output from GWAS pipeline using Phesant derived variables from UKBiobank
+#> 18046 NA
+#> 18048 NA
+#> 20207 I9_OTHHEART
+#> 22249 I9_VHD_EXNONE
+#> 22725 I9_PULMHEART
+#> 23614 <NA>
+#> 24603 FG_OTHHEART
+#> 27414 NA
+#> 33264 FG_PULMHEART
+#> 35220 NA
+#> 35231 I9_OTHILLHEART
+#> 36931 41204#I259: Output from GWAS pipeline using Phesant derived variables from UKBiobank
+#> 37302 I9_OTHILLHEART_EXNONE
+#> 37894 41202#I251: Output from GWAS pipeline using Phesant derived variables from UKBiobank
+#> 38319 I9_IHD
+#> 38448 I9_RHEUFEV
+#> 38602 <NA>
+#> 41994 I9_ISCHHEART
+#> 42095 NA
+#> 42882 I9_SECONDRIGHT
+#> 43747 NA
+#> 45294 <NA>
+#> 46126 I9_VHD
+#> 46689 41204#I258: Output from GWAS pipeline using Phesant derived variables from UKBiobank
+#> mr nsnp doi coverage study_design priority sd
+#> 7958 1 16380466 <NA> <NA> <NA> 0 NA
+#> 10829 1 9851867 <NA> <NA> <NA> 1 NA
+#> 12268 1 15478580 <NA> <NA> <NA> 0 NA
+#> 14221 1 9851867 <NA> <NA> <NA> 1 NA
+#> 14897 1 9455779 <NA> <NA> <NA> 1 NA
+#> 15028 1 16380466 <NA> <NA> <NA> 0 NA
+#> 16883 1 9851867 <NA> <NA> <NA> 1 NA
+#> 18046 1 10894596 <NA> <NA> <NA> 1 NA
+#> 18048 1 9811287 <NA> <NA> <NA> 0 NA
+#> 20207 1 16380466 <NA> <NA> <NA> 0 NA
+#> 22249 1 16380466 <NA> <NA> <NA> 0 NA
+#> 22725 1 16380466 <NA> <NA> <NA> 0 NA
+#> 23614 1 79129 <NA> <NA> <NA> 1 NA
+#> 24603 1 16380466 <NA> <NA> <NA> 0 NA
+#> 27414 1 2415020 <NA> <NA> <NA> 0 NA
+#> 33264 1 16380466 <NA> <NA> <NA> 0 NA
+#> 35220 1 13295130 <NA> <NA> <NA> 0 NA
+#> 35231 1 16380177 <NA> <NA> <NA> 0 NA
+#> 36931 1 9851867 <NA> <NA> <NA> 1 NA
+#> 37302 1 16380466 <NA> <NA> <NA> 0 NA
+#> 37894 1 9851867 <NA> <NA> <NA> 1 NA
+#> 38319 1 16380466 <NA> <NA> <NA> 0 NA
+#> 38448 1 16380466 <NA> <NA> <NA> 0 NA
+#> 38602 1 2420361 <NA> <NA> <NA> 2 NA
+#> 41994 1 16380466 <NA> <NA> <NA> 0 NA
+#> 42095 1 13586589 <NA> <NA> <NA> 0 NA
+#> 42882 1 16380459 <NA> <NA> <NA> 0 NA
+#> 43747 1 13295130 <NA> <NA> <NA> 0 NA
+#> 45294 1 540233 <NA> <NA> <NA> 3 NA
+#> 46126 1 16380358 <NA> <NA> <NA> 0 NA
+#> 46689 1 9851867 <NA> <NA> <NA> 1 NAThe most recent CARDIOGRAM GWAS is ID number ieu-a-7. We
+can extract the BMI SNPs from this GWAS as follows:
+chd_out_dat1 <- extract_outcome_data(
+ snps = bmi_exp_dat$SNP,
+ outcomes = 'ieu-a-7'
+)The extract_outcome_data() function is flexible. The
+snps argument only requires an array of rsIDs, and the
+outcomes argument can be a vector of outcomes, e.g.
+chd_out_dat2 <- extract_outcome_data(
+ snps = c("rs234", "rs17097147"),
+ outcomes = c('ieu-a-2', 'ieu-a-7')
+)will extract the two SNPs from each of the outcomes
+ieu-a-2 and ieu-a-7.
+
+LD proxies +
+By default if a particular requested SNP is not present in the +outcome GWAS then a SNP (proxy) that is in LD with the requested SNP +(target) will be searched for instead. LD proxies are defined using 1000 +genomes European sample data. The effect of the proxy SNP on the outcome +is returned, along with the proxy SNP, the effect allele of the proxy +SNP, and the corresponding allele (in phase) for the target SNP.
+The parameters for handling LD proxies are as follows:
+-
+
-
+
proxies= TRUE or FALSE (TRUE by default)
+ -
+
rsq= numeric value of minimum rsq to find a proxy. +Default is 0.8, minimum is 0.6
+ -
+
palindromes= Allow palindromic SNPs? Default is 1 +(yes)
+ -
+
maf_threshold= If palindromes allowed then what is the +maximum minor allele frequency of palindromes allowed? Default is +0.3.
+
+
+
+Using local GWAS summary data +
+If you have GWAS summary data that is not present in IEU GWAS +database, this can still be used to perform analysis.
+Supposing there is a GWAS summary file called “gwas_summary.csv” with +e.g. 2 million rows and it looks like this:
+rsid,effect,SE,a1,a2,a1_freq,p-value,Units,Gene,n
+rs10767664,0.19,0.030612245,A,T,0.78,5.00E-26,kg/m2,BDNF,225238
+rs13078807,0.1,0.020408163,G,A,0.2,4.00E-11,kg/m2,CADM2,221431
+rs1514175,0.07,0.020408163,A,G,0.43,8.00E-14,kg/m2,TNNI3K,207641
+rs1558902,0.39,0.020408163,A,T,0.42,5.00E-120,kg/m2,FTO,222476
+...
+...To extract the exposure SNPs from this data, we would use the +following command:
+
+outcome_dat <- read_outcome_data(
+ snps = bmi_exp_dat$SNP,
+ filename = "gwas_summary.csv",
+ sep = ",",
+ snp_col = "rsid",
+ beta_col = "effect",
+ se_col = "SE",
+ effect_allele_col = "a1",
+ other_allele_col = "a2",
+ eaf_col = "a1_freq",
+ pval_col = "p-value",
+ units_col = "Units",
+ gene_col = "Gene",
+ samplesize_col = "n"
+)This returns an outcome data frame with only the SNPs that were +requested (if those SNPs were present in the “gwas_summary.csv” +file).
+
+
+Outcome data format +
+The extract_outcome_data function returns a table of SNP
+effects for the requested SNPs on the requested outcomes. The format of
+the data is similar to the exposure data format, except the main columns
+are as follows:
-
+
SNP
+beta.outcome
+se.outcome
+samplesize.outcome
+ncase.outcome
+ncontrol.outcome
+pval.outcome
+eaf.outcome
+effect_allele.outcom
+other_allele.outcome
+units.outcome
+outcome
+consortium.outcome
+year.outcome
+pmid.outcome
+id.outcome
+originalname.outcome
+proxy.outcome
+target_snp.outcome
+proxy_snp.outcome
+target_a1.outcome
+target_a2.outcome
+proxy_a1.outcome
+proxy_a2.outcome
+mr_keep.outcome
+data_source.outcome
+
+
+ More advanced use of local data +
+We have developed a summary data format called “GWAS VCF”, which is +designed to store GWAS results in a strict and performant way. It is +possible to use this format with the TwoSampleMR package. Going down +this avenue also allows you to use LD proxy functionality using your own +LD reference files (or ones that we provide). For more details, see this +package that explains the format and how to query it in R:
+https://github.com/mrcieu/gwasvcf
+and this package for how to connect the data to other packages +including TwoSampleMR
+ +
+
+
+
+
+
+
+
+
+
+
+
+
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+
+
+
+
+
+
+
+
+
+
+
+
+
+
+Perform MR
+Gibran Hemani +and Philip Haycock
+ + + Source:vignettes/perform_mr.Rmd
+ perform_mr.Rmd
+
+
+
+
+Introduction +
+Let’s continue with the example of BMI on CHD:
+
+bmi_exp_dat <- extract_instruments(outcomes = 'ieu-a-2')
+chd_out_dat <- extract_outcome_data(snps = bmi_exp_dat$SNP, outcomes = 'ieu-a-7')
+dat <- harmonise_data(bmi_exp_dat, chd_out_dat)
+#> Harmonising Body mass index || id:ieu-a-2 (ieu-a-2) and Coronary heart disease || id:ieu-a-7 (ieu-a-7)Once the exposure and outcome data are harmonised, we have effects +and standard errors for each instrument SNP available for the exposure +and outcome traits. We can use this information to perform Mendelian +randomisation. To do this, simply run:
+
+res <- mr(dat)
+#> Analysing 'ieu-a-2' on 'ieu-a-7'
+res
+#> id.exposure id.outcome outcome
+#> 1 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 2 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 3 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 4 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 5 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> exposure method nsnp b
+#> 1 Body mass index || id:ieu-a-2 MR Egger 79 0.5024935
+#> 2 Body mass index || id:ieu-a-2 Weighted median 79 0.3870065
+#> 3 Body mass index || id:ieu-a-2 Inverse variance weighted 79 0.4459091
+#> 4 Body mass index || id:ieu-a-2 Simple mode 79 0.3401554
+#> 5 Body mass index || id:ieu-a-2 Weighted mode 79 0.3790910
+#> se pval
+#> 1 0.14396056 8.012590e-04
+#> 2 0.07639889 4.071091e-07
+#> 3 0.05898302 4.032020e-14
+#> 4 0.15001315 2.612742e-02
+#> 5 0.10221374 3.881092e-04This returns a data frame of estimates of the causal effect of the +exposure on the outcome for a range of different MR methods.
+If there were multiple exposures against multiple outcomes in
+dat, the mr() function will perform each MR
+method for each combination of exposure-outcome traits.
+
+
+
+
+MR methods +
+The list of available MR methods can be obtained:
+
+mr_method_list()
+#> obj
+#> 1 mr_wald_ratio
+#> 2 mr_two_sample_ml
+#> 3 mr_egger_regression
+#> 4 mr_egger_regression_bootstrap
+#> 5 mr_simple_median
+#> 6 mr_weighted_median
+#> 7 mr_penalised_weighted_median
+#> 8 mr_ivw
+#> 9 mr_ivw_radial
+#> 10 mr_ivw_mre
+#> 11 mr_ivw_fe
+#> 12 mr_simple_mode
+#> 13 mr_weighted_mode
+#> 14 mr_weighted_mode_nome
+#> 15 mr_simple_mode_nome
+#> 16 mr_raps
+#> 17 mr_sign
+#> 18 mr_uwr
+#> name PubmedID
+#> 1 Wald ratio
+#> 2 Maximum likelihood
+#> 3 MR Egger 26050253
+#> 4 MR Egger (bootstrap) 26050253
+#> 5 Simple median
+#> 6 Weighted median
+#> 7 Penalised weighted median
+#> 8 Inverse variance weighted
+#> 9 IVW radial
+#> 10 Inverse variance weighted (multiplicative random effects)
+#> 11 Inverse variance weighted (fixed effects)
+#> 12 Simple mode
+#> 13 Weighted mode
+#> 14 Weighted mode (NOME)
+#> 15 Simple mode (NOME)
+#> 16 Robust adjusted profile score (RAPS)
+#> 17 Sign concordance test
+#> 18 Unweighted regression
+#> Description use_by_default
+#> 1 TRUE
+#> 2 FALSE
+#> 3 TRUE
+#> 4 FALSE
+#> 5 FALSE
+#> 6 TRUE
+#> 7 FALSE
+#> 8 TRUE
+#> 9 FALSE
+#> 10 FALSE
+#> 11 FALSE
+#> 12 TRUE
+#> 13 TRUE
+#> 14 FALSE
+#> 15 FALSE
+#> 16 FALSE
+#> 17 Tests for concordance of signs between exposure and outcome FALSE
+#> 18 Doesn't use any weights FALSE
+#> heterogeneity_test
+#> 1 FALSE
+#> 2 TRUE
+#> 3 TRUE
+#> 4 FALSE
+#> 5 FALSE
+#> 6 FALSE
+#> 7 FALSE
+#> 8 TRUE
+#> 9 TRUE
+#> 10 FALSE
+#> 11 FALSE
+#> 12 FALSE
+#> 13 FALSE
+#> 14 FALSE
+#> 15 FALSE
+#> 16 FALSE
+#> 17 FALSE
+#> 18 TRUETo perform them, they can be specified in the mr()
+function, e.g. to only perform MR Egger regression and Inverse variance
+weighted methods,
+mr(dat, method_list = c("mr_egger_regression", "mr_ivw"))
+#> Analysing 'ieu-a-2' on 'ieu-a-7'
+#> id.exposure id.outcome outcome
+#> 1 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 2 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> exposure method nsnp b
+#> 1 Body mass index || id:ieu-a-2 MR Egger 79 0.5024935
+#> 2 Body mass index || id:ieu-a-2 Inverse variance weighted 79 0.4459091
+#> se pval
+#> 1 0.14396056 8.01259e-04
+#> 2 0.05898302 4.03202e-14By default, all the methods that are labelled TRUE in
+the use_by_default column are used by the mr()
+function.
+
+
+Sensitivity analyses +
+
+
+
+
+Heterogeneity statistics +
+Some of the MR methods can also perform tests for heterogeneity. To +obtain those statistics:
+
+mr_heterogeneity(dat)
+#> id.exposure id.outcome outcome
+#> 1 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 2 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> exposure method Q Q_df
+#> 1 Body mass index || id:ieu-a-2 MR Egger 143.3046 77
+#> 2 Body mass index || id:ieu-a-2 Inverse variance weighted 143.6508 78
+#> Q_pval
+#> 1 6.841585e-06
+#> 2 8.728420e-06As with the mr() function, the
+mr_heterogeneity() function can take an argument to only
+perform heterogeneity tests using specified methods, e.g.
+mr_heterogeneity(dat, method_list = c("mr_egger_regression", "mr_ivw"))
+#> id.exposure id.outcome outcome
+#> 1 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 2 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> exposure method Q Q_df
+#> 1 Body mass index || id:ieu-a-2 MR Egger 143.3046 77
+#> 2 Body mass index || id:ieu-a-2 Inverse variance weighted 143.6508 78
+#> Q_pval
+#> 1 6.841585e-06
+#> 2 8.728420e-06
+
+
+Horizontal pleiotropy +
+The intercept term in MR Egger regression can be a useful indication +of whether directional horizontal pleiotropy is driving the results of +an MR analysis. This can be obtained as follows:
+
+mr_pleiotropy_test(dat)
+#> id.exposure id.outcome outcome
+#> 1 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> exposure egger_intercept se pval
+#> 1 Body mass index || id:ieu-a-2 -0.001719304 0.003985962 0.6674266
+
+
+
+
+Single SNP analysis +
+To obtain the MR estimates using each of the SNPs singly we can do +the following:
+
+res_single <- mr_singlesnp(dat)This returns a data.frame of results that is similar to the output
+from mr() except it performs the analysis multiple times
+for each exposure-outcome combination - each time using a different
+single SNP to perform the analysis.
The method used to perform the single SNP MR is the Wald ratio by +default, though this can be changed, e.g. to use the fixed effects meta +analysis method instead:
+
+res_single <- mr_singlesnp(dat, single_method = "mr_meta_fixed")The mr_singlesnp() function calculates the full MR using
+all available SNPs as well, and by default it uses the IVW and MR Egger
+methods. This can be specified as so:
+res_single <- mr_singlesnp(dat, all_method = "mr_two_sample_ml")will perform only the maximum likelihood method for the combined +test.
+
+
+
+
+Leave-one-out analysis +
+It is possible to perform a leave-one-out analysis, where the MR is +performed again but leaving out each SNP in turn, to identify if a +single SNP is driving the association.
+
+res_loo <- mr_leaveoneout(dat)By default the method used is the inverse variance weighted method,
+but this can be changed by using the method argument.
+
+
+Plots +
+There are a few ways to visualise the results, listed below
+
+
+
+
+
+
+
+
+Scatter plot +
+We can depict the relationship of the SNP effects on the exposure +against the SNP effects on the outcome using a scatter plot.
+
+res <- mr(dat)
+#> Analysing 'ieu-a-2' on 'ieu-a-7'
+p1 <- mr_scatter_plot(res, dat)A scatter plot is created for each exposure-outcome test, and stored
+in p1 as a list of plots. For example, to plot the first
+scatter plot:
+p1[[1]]
And to see how many plots there are:
+
+length(p1)
+#> [1] 1Lines are drawn for each method used in mr(dat), the
+slope of the line corresponding to the estimated causal effect. To limit
+which lines are drawn, simply specify the desired methods, e.g. to only
+draw MR Egger and IVW:
+res <- mr(dat, method_list = c("mr_egger_regression", "mr_ivw"))
+#> Analysing 'ieu-a-2' on 'ieu-a-7'
+p1 <- mr_scatter_plot(res, dat)It is possible to save this plot using the ggsave()
+function from the ggplot2 package, e.g. to save as a
+pdf
+ggsave(p1[[1]], file = "filename.pdf", width = 7, height = 7)or save as a png
+
+ggsave(p1[[1]], file = "filename.png", width = 7, height = 7)See ?ggplot2::ggsave for more info.
+
+
+
+Forest plot +
+Use the mr_forest_plot() function to compare the MR
+estimates using the different MR methods against the single SNP
+tests.
+res_single <- mr_singlesnp(dat)
+p2 <- mr_forest_plot(res_single)
+p2[[1]]
Here, the plot shows the causal effect as estimated using each of the +SNPs on their own, and comparing against the causal effect as estimated +using the methods that use all the SNPs.
+To get plots that use different methods, specify them in the
+mr_singlesnp() function:
+res_single <- mr_singlesnp(dat, all_method = c("mr_ivw", "mr_two_sample_ml"))
+p2 <- mr_forest_plot(res_single)
+p2[[1]]
+
+
+Leave-one-out plot +
+Use the mr_leaveoneout_plot() function to visualise the
+leave-one-out analysis:
+res_loo <- mr_leaveoneout(dat)
+p3 <- mr_leaveoneout_plot(res_loo)
+p3[[1]]
Specify the test to use
+e.g. mr_leaveoneout(dat, method = mr_egger_regression) to
+use MR-Egger regression.
+
+
+Funnel plot +
+Asymmetry in a funnel plot is useful for gauging the reliability of a +particular MR analysis. Funnel plots can be produced using the single +SNP results as follows:
+
+res_single <- mr_singlesnp(dat)
+p4 <- mr_funnel_plot(res_single)
+p4[[1]]
+
+1-to-many forest plot +
+A 1-to-many MR analysis interrogates the effect of a single exposure
+on multiple outcomes or multiple exposures on a single outcome. The
+results of this analysis can be visualised using the 1-to-many forest
+plot, with or without stratification on a categorical variable. From a
+visual point of view, the function works best for 50 or fewer results
+and is not really designed to handle more than a 100 results. If your
+number of results is much greater than 50, it may be better to split
+these across two separate plots. For example, if you have 100 sets of
+results you could divide these equally across two plots and then combine
+the two plots together in another programme like Powerpoint. The
+function assumes the results are already in the right order for
+plotting. As such, users are advised to sort their results according to
+how they would like them to appear in the plot. Users can use their own
+code to do this or they can use the sort_1_to_many()
+function.
+
+
+Step 1: generate 1-to-many MR results +
+
+exp_dat <- extract_instruments(outcomes = c(2, 100, 1032, 104, 1, 72, 999))
+table(exp_dat$exposure)
+chd_out_dat <- extract_outcome_data(
+ snps = exp_dat$SNP,
+ outcomes = 7
+)
+
+dat2 <- harmonise_data(
+ exposure_dat = exp_dat,
+ outcome_dat = chd_out_dat
+)
+res <- mr(dat2)
+
+Step 2. Make the 1-to-many forest plot +
+
+
+
+
+
+Example 1. Effect of multiple risk factors on coronary heart +disease +
+In this example we wish to plot results from an MR analysis of the +effect of multiple exposures on coronary heart disease, with results +sorted by decreasing effect size (largest effect at the top of the plot) +and with one MR method for each unique exposure-outcome combination. We +will also make the size of each point estimate proportional to its +inverse variance. This is a useful way to draw attention towards the +most reliable results and away from results with very wide confidence +intervals. To specify the size of the point estimate, set the weight +argument to the name of the column in the data with the weight +information.
+
+res <- subset_on_method(res) # default is to subset on either the IVW method (>1 instrumental SNP) or Wald ratio method (1 instrumental SNP).
+res <- sort_1_to_many(res, b = "b", sort_action = 4) # this sorts results by decreasing effect size (largest effect at top of the plot)
+res <- split_exposure(res) # to keep the Y axis label clean we exclude the exposure ID labels from the exposure column
+res$weight <- 1/res$se
+
+min(exp(res$b - 1.96*res$se)) # identify value for 'lo' in forest_plot_1_to_many
+max(exp(res$b + 1.96*res$se)) # identify value for 'up' in forest_plot_1_to_many
+
+forest_plot_1_to_many(
+ res,
+ b = "b",
+ se = "se",
+ exponentiate = TRUE,
+ ao_slc = FALSE,
+ lo = 0.3,
+ up = 2.5,
+ TraitM = "exposure",
+ col1_width = 2,
+ by = NULL,
+ trans = "log2",
+ xlab = "OR for CHD per SD increase in risk factor (95% confidence interval)",
+ weight = "weight"
+)It is also possible to add additional columns and column titles and +to choose the size of the text in the columns:
+
+res$pval<-formatC(res$pval, format = "e", digits = 2)
+forest_plot_1_to_many(
+ res,
+ b = "b",
+ se = "se",
+ exponentiate = TRUE,
+ ao_slc = FALSE,
+ lo = 0.3,
+ up = 2.5,
+ TraitM = "exposure",
+ by = NULL,
+ trans = "log2",
+ xlab = "OR for CHD per SD increase in risk factor (95% CI)",
+ weight = "weight",
+ subheading_size = 11,
+ col1_title = "Risk factor",
+ col1_width = 2.5,
+ col_text_size = 4,
+ addcols = c("nsnp", "pval"),
+ addcol_widths = c(1.0, 1.0),
+ addcol_titles = c("No. SNPs", "P-val")
+)In my own workflow I prefer to to keep the plot free of axis and +column titles and to add them separately in a program like +powerpoint:
+
+forest_plot_1_to_many(
+ res,
+ b = "b",
+ se = "se",
+ exponentiate = TRUE,
+ ao_slc = FALSE,
+ lo = 0.3,
+ up = 3.0,
+ TraitM = "exposure",
+ col1_width = 2.0,
+ by = NULL,
+ trans = "log2",
+ xlab = "",
+ addcols = c("nsnp", "pval"),
+ weight = "weight",
+ col_text_size = 4,
+ addcol_widths = c(0.5, 1.0),
+ addcol_titles = c("", "")
+)
+
+
+Example 2. MR results for multiple MR methods grouped by multiple +exposures +
+In this next example we plot the results from an analysis of the +effect of multiple exposures on coronary heart disease using multiple +methods, with results grouped by exposure. We also want the result for +the IVW method to be given priority and to go above the other methods. +We also want the exposure with the largest IVW effect size to go the top +of the plot. We also set the TraitM argument to the column describing +the MR method. This is because we are grouping the results on the +exposures. Normally the row labels would correspond to the exposures but +in this example we want the row names to correspond to the MR +method.
+
+res <- mr(dat2)
+res <- split_exposure(res) # to keep the Y axis label clean we exclude the exposure ID labels from the exposure column
+
+res <-
+ sort_1_to_many(
+ res,
+ group = "exposure",
+ sort_action = 3,
+ priority = "Inverse variance weighted",
+ trait_m = "method"
+ )
+
+forest_plot_1_to_many(
+ res,
+ b = "b",
+ se = "se",
+ exponentiate = TRUE,
+ trans = "log2",
+ ao_slc = FALSE,
+ lo = 0.03,
+ up = 22,
+ col1_width = 2,
+ by = "exposure",
+ TraitM = "method",
+ xlab = "OR for CHD per SD increase in risk factor (95% confidence interval)",
+ subheading_size = 12,
+ col_text_size = 4
+)
+
+
+Example 3. Stratify results on a grouping variable +
+In this next example we plot the same results as above but with +results stratified by a grouping variable. We also select one MR method +for each unique exposure-outcome combination and sort the results by +decreasing effect size within each group (i.e. largest effect at the +top).
+
+res <- mr(dat2)
+res <- split_exposure(res)
+res <- subset_on_method(res)
+res$subcategory[res$exposure %in% c("Adiponectin", "Hip circumference", "Waist circumference")] <- "Group 1"
+res$subcategory[is.na(res$subcategory)] <- "Group 2"
+res$weight <- 1/res$se
+res <- sort_1_to_many(res, sort_action = 1, group = "subcategory")
+
+forest_plot_1_to_many(
+ res,
+ b = "b",
+ se = "se",
+ exponentiate = TRUE,
+ trans = "log2",
+ ao_slc = FALSE,
+ lo = 0.3,
+ up = 2.5,
+ TraitM = "exposure",
+ col_text_size = 4,
+ col1_width = 1.5,
+ by = "subcategory",
+ xlab = "OR for CHD per SD increase in risk factor (95% confidence interval)",
+ subheading_size = 14,
+ weight = "weight"
+)In the above example we made up an arbitrary grouping variable called +“subcategory” with values “Group 1” and “Group 2”. Typically, however, +the grouping variable might correspond to something like a trait +ontology (e.g. anthropometric and glycemic traits) or study design +(e.g. MR and observational studies).
+
+
+
+
+
+Example 4. Effect of BMI on 103 diseases +
+The plot function works best with 50 or fewer rows and is not really +designed to handle more than a 100. Visualising a single-column forest +plot with 100 results is also quite difficult. If your number of results +is much greater than 50, it is advisable to split the results across two +different plots. In the example below we select BMI as the exposure and +test this against 103 diseases in the IEU GWAS database:
+
+exp_dat <- extract_instruments(outcomes = 2) # extract instruments for BMI
+ao <- available_outcomes()
+ao <- ao[ao$category == "Disease", ] # identify diseases
+ao <- ao[which(ao$ncase > 100), ]
+
+dis_dat <- extract_outcome_data(
+ snps = exp_dat$SNP,
+ outcomes = ao$id
+)
+
+dat3 <- harmonise_data(
+ exposure_dat = exp_dat,
+ outcome_dat = dis_dat
+)
+
+res <- mr(dat3, method_list = c("mr_wald_ratio", "mr_ivw"))
+res <- split_outcome(res) # to keep the Y axis label clean we exclude the exposure ID labels from the exposure column
+
+res <- sort_1_to_many(res, b = "b", sort_action = 4) # this sorts results by decreasing effect size (largest effect at top of the plot)MR results for 103 diseases can be difficult to visualise in a
+single-column forest plot. In my own workflow I would split these across
+two plots and then join them together in a separate program, such as
+Powerpoint, and do further refinements there. I typically save my plots
+using the pdf() graphics device. In this particular example
+the disease labels probably require some cleaning up (some are a bit
+long) or alternatively the column text size could be made smaller. It is
+also possible to change the colour of the plot and the shape of the
+point estimates. Type ?forest_plot_1_to_many for further
+details.
+res1 <- res[1:52, ]
+res2 <- res[53:103, ]
+
+plot1 <- forest_plot_1_to_many(
+ res1,
+ b = "b",
+ se = "se",
+ exponentiate = TRUE,
+ trans = "log2",
+ ao_slc = FALSE,
+ lo = 0.004,
+ up = 461,
+ col1_width = 2,
+ TraitM = "outcome",
+ col_text_size = 3,
+ xlab = ""
+)
+
+plot2 <- forest_plot_1_to_many(
+ res2,
+ b = "b",
+ se = "se",
+ exponentiate = TRUE,
+ trans = "log2",
+ ao_slc = FALSE,
+ lo = 0.004,
+ up = 461,
+ col1_width = 2,
+ TraitM = "outcome",
+ subheading_size = 11,
+ col_text_size = 3,
+ xlab = ""
+)
+
+plot1
+plot2
+
+pdf("plot1.pdf", height = 10, width = 8)
+plot1
+dev.off()+
+
+
+
+MR.RAPS: Many weak instruments analysis +
+MR.RAPS (Robust Adjusted Profile Score) is a recently proposed method +that considers the measurement error in SNP-exposure effects, is +unbiased when there are many (e.g. hundreds of) weak instruments, and is +robust to systematic and idiosyncratic pleiotropy. See the arXiv preprint for more +detail about the statistical methodology.
+MR.RAPS is implemented in the R package mr.raps that is +available on CRAN. It can be directly called from TwoSampleMR by
+ +MR.RAPS comes with two main options: over.dispersion
+(whether the method should consider systematic pleiotropy) and
+loss.function (either "l2",
+"huber", or "tukey"). The latter two loss
+functions are robust to idiosyncratic pleiotropy. The default option is
+over.dispersion = TRUE and
+loss.function = "tukey". To change these options, modify
+the parameters argument of mr() by (for
+example)
+res <-
+ mr(
+ dat,
+ method_list = c("mr_raps"),
+ parameters = list(over.dispersion = FALSE, loss.function = "l2")
+ )+
+
+
+
+Reports +
+A report can be generated that performs all MR analyses, sensitivity +analyses, and plots, and presents them in a single self-contained html +web page, word document, or pdf document.
+
+mr_report(dat)By default this produces a html file in the current working +directory, but see the help pages on how to modify this.
+This function will create a separate report file for every
+exposure-outcome combination that is present in the dat
+object.
+
+
+
+
+
+
+
+MR Steiger directionality test +
+This is an implementation of the method described here:
+ +In MR it is assumed that the instruments influence the exposure first +and then the outcome through the exposure. But sometimes this is +difficult to evaluate, for example is a cis-acting SNP influencing gene +expression levels or DNA methylation levels first? The causal direction +between the hypothesised exposure and outcomes can be tested using the +Steiger test (Hemani, Tilling, and Davey Smith +2017). For example:
+
+out <- directionality_test(dat)
+#> r.exposure and/or r.outcome not present.
+#> Calculating approximate SNP-exposure and/or SNP-outcome correlations, assuming all are quantitative traits. Please pre-calculate r.exposure and/or r.outcome using get_r_from_lor() for any binary traits
+knitr::kable(out)| id.exposure | +id.outcome | +exposure | +outcome | +snp_r2.exposure | +snp_r2.outcome | +correct_causal_direction | +steiger_pval | +
|---|---|---|---|---|---|---|---|
| ieu-a-2 | +ieu-a-7 | +Body mass index || id:ieu-a-2 | +Coronary heart disease || id:ieu-a-7 | +0.0158082 | +0.0013505 | +TRUE | +0 | +
It calculates the variance explained in the exposure and the outcome +by the instrumenting SNPs, and tests if the variance in the outcome is +less than the exposure.
+This test is, like many others, liable to give inaccurate causal +directions under some measurement error parameters in the exposure and +the outcome (e.g. if the outcome has much lower measurement precision +then its proportion of variance explained will be underestimated). +Sensitivity can be applied to evaluate the extent to which the inferred +causal direction is liable to measurement error, in two ways.
+-
+
- Provide estimates of measurement error for the exposure and the +outcome, and obtain an adjusted estimate of the causal direction +
- For all possible values of measurement error, identify the +proportion of the parameter space which supports the inferred causal +direction +
These tests are obtained using:
+
+mr_steiger(
+ p_exp = dat$pval.exposure,
+ p_out = dat$pval.outcome,
+ n_exp = dat$samplesize.exposure,
+ n_out = dat$samplesize.outcome,
+ r_xxo = 1,
+ r_yyo = 1,
+ r_exp=0
+)+
+
+
+
+
+
+
+Multivariable MR +
+When SNPs instrument multiple potential exposures, for example in the +case of different lipid fractions, one method for overcoming this +problem is to estimate the influence of each lipid conditioning on the +effects of the SNPs on the other lipids. Multivariable MR can be +performed using the R package as follows. Practically speaking, this is +the process that needs to occur from the perspective of generating the +data in the correct format:
+-
+
- Get instruments for each exposure +
- Combine these into a set of all instruments +
- Clump these to avoid the possibility that e.g. a variant for +exposure 1 is in LD with a variant for exposure 2 +
- Re-extract all the final clumped SNPs from (3) from all of the +exposures +
- Harmonise them all to be on the same effect allele +
- Use the multivariable MR method against these harmonised data +
Example - The GWAS IDs for HDL, LDL and total cholesterol are
+ieu-a-299, ieu-a-300 and
+ieu-a-302. The GWAS ID for coronary heart disease (CHD) is
+ieu-a-7. In this example we will estimate the multivariable
+effects of HDL, LDL and total cholesterol on CHD.
+id_exposure <- c("ieu-a-299", "ieu-a-300", "ieu-a-302")
+id_outcome <- "ieu-a-7"First obtain the instruments for each lipid fraction. This entails +obtaining a combined set of SNPs including all instruments, and getting +those SNPs for each lipid fraction. Therefore, if there are e.g. 20 +instruments for each of 3 lipid fractions, but combined there are 30 +unique SNPs, then we need to extract each of the 30 SNPs from each lipid +fraction (exposure).
+
+mv_exposure_dat <- mv_extract_exposures(id_exposure)Next, also extract those SNPs from the outcome.
+
+mv_outcome_dat <- extract_outcome_data(exposure_dat$SNP, id_outcome)Once the data has been obtained, harmonise so that all are on the +same reference allele.
+
+mvdat <- mv_harmonise_data(mv_exposure_dat, mv_outcome_dat)
+#> Harmonising HDL cholesterol || id:ieu-a-299 (ieu-a-299) and Coronary heart disease || id:ieu-a-7 (ieu-a-7)Finally, perform the multivariable MR analysis
+
+res <- mv_multiple(mvdat)This generates a table of results.
+
+
+Note about MV methods +
+There are several different ways in which this analysis can be +formulated. e.g. consider 3 exposures against one outcome, one +could:
+-
+
- Fit all exposures together or fit one exposure at a time against the
+residuals of the outcome that has been adjusted for the other outcomes.
+The former is recommended by default in this R package through the
+
mv_multiple()function but the latter was how MV MR was +originally described by Burgess et al 2015 and can be done with +mv_residual().
+ - Fitting all instruments for all exposures (default) or only fitting +the instruments for each exposure sequentially +
- Forcing the slopes through the origin (default) or allowing an +intercept term. +
With these three different parameters there are eight different ways +to do MV analysis. We recommend the default settings as described +above.
+
+
+Note about visualisation +
+Plots can be generated using the plots = TRUE argument
+for mv_multiple() and mv_residual().
The current plots being generated are not necessarily adequate +because while they show the slope through the raw points, they do not +demonstrate that the raw points might be effectively different between +plots because they are conditional on the other exposures.
+
+
+
+Using your own summary data +
+If you want to perform analysis with your local summary data
+(i.e. not in the OpenGWAS database) then use then look up the
+mv_extract_exposures_local() function instead of the
+mv_extract_exposures() function.
+
+
+
+
+
+
+
+
+MR estimates when instruments are correlated +
+In the examples shown so far it is assumed that instruments are +independent (i.e. they are not in linkage disequilibrium, LD). This is +to avoid ‘double counting’ effects. An alternative approach is to +estimate the MR effects accounting for the correlation between +variants.
+The TwoSampleMR package has not implemented this yet, but the MendelianRandomization +R package by Olena Yavorska and Stephen Burgess does have this +functionality. We can use the TwoSampleMR package to extract, format and +harmonise data, and then convert to the format required by the +MendelianRandomization package. The IEU GWAS database server has the +individual level genetic data for ~500 Europeans in 1000 genomes data, +and can obtain the LD matrix for a set of SNPs using these data. For +example:
+ +
+ld_mat
+#> rs234_A_G rs1205_T_C
+#> rs234_A_G 1.0000000 0.0797023
+#> rs1205_T_C 0.0797023 1.0000000Here ld_matrix() returns the LD correlation values (not
+R2) for each pair of variants present in the 1000 genomes
+data set.
+dat <- harmonise_data(
+ exposure_dat = bmi_exp_dat,
+ outcome_dat = chd_out_dat
+)
+#> Harmonising Body mass index || id:ieu-a-2 (ieu-a-2) and Coronary heart disease || id:ieu-a-7 (ieu-a-7)Convert to the MRInput format for the
+MendelianRandomization package:
+dat2 <- dat_to_MRInput(dat)
+#> Converting:
+#> - exposure: Body mass index || id:ieu-a-2
+#> - outcome: Coronary heart disease || id:ieu-a-7This produces a list of MRInput objects that can be used
+with the MendelianRandomization functions, e.g.
+MendelianRandomization::mr_ivw(dat2[[1]])
+#>
+#> Inverse-variance weighted method
+#> (variants uncorrelated, random-effect model)
+#>
+#> Number of Variants : 79
+#>
+#> ------------------------------------------------------------------
+#> Method Estimate Std Error 95% CI p-value
+#> IVW 0.446 0.059 0.330, 0.562 0.000
+#> ------------------------------------------------------------------
+#> Residual standard error = 1.357
+#> Heterogeneity test statistic (Cochran's Q) = 143.6508 on 78 degrees of freedom, (p-value = 0.0000). I^2 = 45.7%.
+#> F statistic = 65.6.Alternatively, convert to the MRInput format but also
+obtaining the LD matrix for the instruments
+dat2 <- try(dat_to_MRInput(dat, get_correlation = TRUE))
+#> Converting:
+#> - exposure: Body mass index || id:ieu-a-2
+#> - outcome: Coronary heart disease || id:ieu-a-7
+#> - obtaining LD matrix
+#> Please look at vignettes for options on running this locally if you need to run many instances of this command.
+#> Warning in ieugwasr::ld_matrix(variants = snps, with_alleles = with_alleles, : The following variants are not present in the LD reference panel
+#> rs2033529
+if (class(dat2) != "try-error") MendelianRandomization::mr_ivw(dat2[[1]], correl = TRUE)
+#>
+#> Inverse-variance weighted method
+#> (variants correlated, random-effect model)
+#>
+#> Number of Variants : 78
+#>
+#> ------------------------------------------------------------------
+#> Method Estimate Std Error 95% CI p-value
+#> IVW 0.441 0.056 0.331, 0.551 0.000
+#> ------------------------------------------------------------------
+#> Residual standard error = 1.414
+#> Heterogeneity test statistic (Cochran's Q) = 153.8519 on 77 degrees of freedom, (p-value = 0.0000). I^2 = 50.0%.
+#> F statistic = 80.3.
+#>
+#> (Estimates with correlated variants are sensitive to the signs in the correlation matrix
+#> - please ensure that your correlations are expressed with respect to the same effect alleles as your summarized association estimates.)+
+
+
+
+MR-MoE: Using a mixture of experts machine learning approach +
+We recently developed MR-MoE, a method to choose the most appropriate +amongst several MR tests using a machine learning algorithm. Note that +the method is still under review, but full details are described here: +https://doi.org/10.1101/173682.
+MR-MoE operates by taking a set of harmonised data, inferring some +characteristics about the dataset, and using those characteristics to +predict how well each of the different MR methods will perform on the +dataset, in terms of maximising power while minimising false discovery +rates.
+In order to run the analysis you must download an RData object that +contains the trained random forests that are used to predict the +efficacy of each method. This can be downloaded from here:
+ +Caution: this is a large file (approx 167Mb)
+Once downloaded, read in the object and use the mr_moe()
+function to perform the analysis. An example is shown here, estimating
+the causal effect of BMI on coronary heart disease:
+# Extact instruments for BMI
+exposure_dat <- extract_instruments("ieu-a-2")
+
+# Get corresponding effects for CHD
+outcome_dat <- extract_outcome_data(exposure_dat$SNP, "ieu-a-7")
+
+# Harmonise
+dat <- harmonise_data(exposure_dat, outcome_dat)
+
+# Load the downloaded RData object. This loads the rf object
+load("rf.rdata")
+
+# Obtain estimates from all methods, and generate data metrics
+res_all <- mr_wrapper(dat)
+
+# MR-MoE - predict the performance of each method
+res_moe <- mr_moe(res_all, rf)The function does the following:
+-
+
- Performs MR using each of 11 MR methods +
- Applies Steiger filtering or heterogeneity filtering or both to +remove SNPs that do not have substantially larger R2 with the +exposure than the outcome. Note - for binary traits ensure number of +cases, number of controls, and allele frequencies are available for each +SNP. For continuous traits make sure the p-value and sample size is +available. The function infers if a trait is binary or continuous based +on the units.exposure and units.outcome columns - binary traits must +have those values set to ‘log odds’ +
- Performs the 14 MR methods again but using the subset of SNPs that +survive Steiger filtering +
- Generates meta data about the summary data to predict the most +reliable of the 28 methods applied. +
For every exposure / outcome combination in the dat
+object, the MR-MoE method is applied. The function returns a list which
+is as long as the number of exposure / outcome combinations. In this
+case, it will be of length 1, containing the result for BMI on CHD.
The result object itself is a list with the following elements:
+-
+
-
+
estimates(results from each MR)
+ -
+
heterogeneity(results from heterogeneity for different +filtering approaches)
+ -
+
directional_pleiotropy(egger intercepts)
+ -
+
info(metrics used to generate MOE)
+
Looking at the estimates, we see that there is a column
+called MOE which is the predicted AUROC curve performance
+of each method.
+
+
+Post MR results management +
+The TwoSampleMR package also provides the following functions for +managing or editing MR results.
+
+
+
+
+Split outcome names +
+The outcome column in the output of mr() combines the original +outcome name with the outcome trait ID.
+
+head(res)
+#> $result
+#> id.exposure exposure id.outcome
+#> 1 ieu-a-299 HDL cholesterol || id:ieu-a-299 ieu-a-7
+#> 2 ieu-a-300 LDL cholesterol || id:ieu-a-300 ieu-a-7
+#> 3 ieu-a-302 Triglycerides || id:ieu-a-302 ieu-a-7
+#> outcome nsnp b se pval
+#> 1 Coronary heart disease || id:ieu-a-7 79 -0.08919724 0.05970552 1.351879e-01
+#> 2 Coronary heart disease || id:ieu-a-7 68 0.37853543 0.04976846 2.828614e-14
+#> 3 Coronary heart disease || id:ieu-a-7 42 0.13584165 0.06738291 4.380354e-02The outcome column can be split into separate columns for the id and +outcome name using the split_outcome function:
+
+res <- mr(dat)
+#> Analysing 'ieu-a-2' on 'ieu-a-7'
+split_outcome(res)
+#> id.exposure id.outcome outcome exposure
+#> 1 ieu-a-2 ieu-a-7 Coronary heart disease Body mass index || id:ieu-a-2
+#> 2 ieu-a-2 ieu-a-7 Coronary heart disease Body mass index || id:ieu-a-2
+#> 3 ieu-a-2 ieu-a-7 Coronary heart disease Body mass index || id:ieu-a-2
+#> 4 ieu-a-2 ieu-a-7 Coronary heart disease Body mass index || id:ieu-a-2
+#> 5 ieu-a-2 ieu-a-7 Coronary heart disease Body mass index || id:ieu-a-2
+#> method nsnp b se pval
+#> 1 MR Egger 79 0.5024935 0.14396056 8.012590e-04
+#> 2 Weighted median 79 0.3870065 0.07717818 5.318417e-07
+#> 3 Inverse variance weighted 79 0.4459091 0.05898302 4.032020e-14
+#> 4 Simple mode 79 0.3401554 0.15276076 2.885059e-02
+#> 5 Weighted mode 79 0.3790910 0.10761091 7.173381e-04
+
+Split exposure names +
+Similarly to the outcome column, the exposure column in the output of
+mr() combines the original exposure name with the exposure
+trait ID. This can be split into separate columns for the id and
+exposure name using the split_exposure function.
+
+
+Generate odds ratios with 95% confidence intervals +
+Users can convert log odds ratios into odds ratios with 95% +confidence intervals using:
+
+generate_odds_ratios(res)
+#> id.exposure id.outcome outcome
+#> 1 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 2 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 3 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 4 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> 5 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> exposure method nsnp b
+#> 1 Body mass index || id:ieu-a-2 MR Egger 79 0.5024935
+#> 2 Body mass index || id:ieu-a-2 Weighted median 79 0.3870065
+#> 3 Body mass index || id:ieu-a-2 Inverse variance weighted 79 0.4459091
+#> 4 Body mass index || id:ieu-a-2 Simple mode 79 0.3401554
+#> 5 Body mass index || id:ieu-a-2 Weighted mode 79 0.3790910
+#> se pval lo_ci up_ci or or_lci95 or_uci95
+#> 1 0.14396056 8.012590e-04 0.22033081 0.7846562 1.652838 1.246489 2.191653
+#> 2 0.07717818 5.318417e-07 0.23573724 0.5382757 1.472566 1.265842 1.713051
+#> 3 0.05898302 4.032020e-14 0.33030238 0.5615158 1.561909 1.391389 1.753328
+#> 4 0.15276076 2.885059e-02 0.04074434 0.6395665 1.405166 1.041586 1.895659
+#> 5 0.10761091 7.173381e-04 0.16817361 0.5900084 1.460956 1.183142 1.804004
+
+
+Subset on method +
+It is sometimes useful to subset results on MR method, so that there +is one unique result for each exposure-outcome combination:
+
+subset_on_method(res)
+#> id.exposure id.outcome outcome
+#> 3 ieu-a-2 ieu-a-7 Coronary heart disease || id:ieu-a-7
+#> exposure method nsnp b
+#> 3 Body mass index || id:ieu-a-2 Inverse variance weighted 79 0.4459091
+#> se pval
+#> 3 0.05898302 4.03202e-14The default is to subset on the IVW method when >1 SNP is +available and to use the Wald ratio method when a single SNP is +available. Users can specify which multi-SNP method to subset on.
+
+
+
+Combine all results +
+It is often useful to combine all results and study level
+characterists into a single dataframe or table, e.g. for sharing results
+with collaborators or when the user wishes to present all results in a
+single table or figure. This can be done using the
+combine_all_mrresults() function:
+res <- mr(dat)
+het <- mr_heterogeneity(dat)
+plt <- mr_pleiotropy_test(dat)
+sin <- mr_singlesnp(dat)
+all_res <-
+ combine_all_mrresults(
+ res,
+ het,
+ plt,
+ sin,
+ ao_slc = TRUE,
+ Exp = TRUE,
+ split.exposure = FALSE,
+ split.outcome = TRUE
+ )
+head(all_res[, c(
+ "Method",
+ "outcome",
+ "exposure",
+ "nsnp",
+ "b",
+ "se",
+ "pval",
+ "intercept",
+ "intercept_se",
+ "intercept_pval",
+ "Q",
+ "Q_df",
+ "Q_pval",
+ "consortium",
+ "ncase",
+ "ncontrol",
+ "pmid",
+ "population"
+)])This combines all results from mr(),
+mr_heterogeneity(), mr_pleiotropy_test() and
+mr_singlesnp() into a single dataframe. It also merges the
+results with outcome study level characteristics from the
+available_outcomes() function, including sample size
+characteristics. If requested, it also exponentiates results (e.g. if
+the user wants log odds ratio converted into odds ratios with 95 percent
+confidence intervals).
+
+ References +
+
+
+
+Hemani, Gibran, Kate Tilling, and George Davey Smith. 2017.
+“Orienting the Causal Relationship Between Imprecisely Measured
+Traits Using GWAS Summary Data.” PLOS Genetics 13 (11):
+e1007081. https://doi.org/10.1371/journal.pgen.1007081.
+
+
+
+
+
+
+
+
+
+
diff --git a/docs/deps/bootstrap-5.3.1/bootstrap.bundle.min.js b/docs/deps/bootstrap-5.3.1/bootstrap.bundle.min.js
new file mode 100644
index 00000000..e8f21f70
--- /dev/null
+++ b/docs/deps/bootstrap-5.3.1/bootstrap.bundle.min.js
@@ -0,0 +1,7 @@
+/*!
+ * Bootstrap v5.3.1 (https://getbootstrap.com/)
+ * Copyright 2011-2023 The Bootstrap Authors (https://github.com/twbs/bootstrap/graphs/contributors)
+ * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)
+ */
+!function(t,e){"object"==typeof exports&&"undefined"!=typeof module?module.exports=e():"function"==typeof define&&define.amd?define(e):(t="undefined"!=typeof globalThis?globalThis:t||self).bootstrap=e()}(this,(function(){"use strict";const t=new Map,e={set(e,i,n){t.has(e)||t.set(e,new Map);const s=t.get(e);s.has(i)||0===s.size?s.set(i,n):console.error(`Bootstrap doesn't allow more than one instance per element. 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+
+
+
+
+
+
+ Authors and Citation
+
+
+
+ Authors
+ +
+
+
+ Citation
+Source: inst/CITATION
Hemani G, Zheng J, Elsworth B, Wade KH, Baird D, Haberland V, Laurin C, Burgess S, Bowden J, Langdon R, Tan VY, Yarmolinsky J, Shihab HA, Timpson NJ, Evans DM, Relton C, Martin RM, Davey Smith G, Gaunt TR, Haycock PC, The MR-Base Collaboration. The MR-Base platform supports systematic causal inference across the human phenome. eLife 2018;7:e34408. doi: 10.7554/eLife.34408
+@Article{twosamplemr,
+ author = {G. Hemani and J. Zheng and B. Elsworth and K. Wade and D. Baird and V. Haberland and C. Laurin and S. Burgess and J. Bowden and R. Langdon and V.Y. Tan and J. Yarmolinsky and H.A. Shibab and N.J. Timpson and D.M. Evans and C. Relton and R.M. Martin and G. {Davey Smith} and T.R. Gaunt and P.C. Haycock and {The MR-Base Collaboration}},
+ title = {The MR-Base platform supports systematic causal inference across the human phenome},
+ year = {2018},
+ volume = {7},
+ journal = {eLife},
+ pages = {e34408},
+ url = {https://elifesciences.org/articles/34408},
+ doi = {10.7554/eLife.34408},
+}
+ Hemani G, Tilling K, Davey Smith G (2017) Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLOS Genetics 13(11): e1007081. https://doi.org/10.1371/journal.pgen.1007081
+@Article{mrsteiger,
+ author = {G. Hemani and K. Tilling and G. {Davey Smith}},
+ title = {Orienting the causal relationship between imprecisely measured traits using GWAS summary data},
+ journal = {PLoS Genetics},
+ year = {2017},
+ volume = {13},
+ number = {11},
+ pages = {e1007081},
+ doi = {10.1371/journal.pgen.1007081},
+ url = {https://doi.org/10.1371/journal.pgen.1007081},
+}
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object[0] : object\n }\n\n if (typeof object === 'string' && object.length > 0) {\n return document.querySelector(parseSelector(object))\n }\n\n return null\n}\n\nconst isVisible = element => {\n if (!isElement(element) || element.getClientRects().length === 0) {\n return false\n }\n\n const elementIsVisible = getComputedStyle(element).getPropertyValue('visibility') === 'visible'\n // Handle `details` element as its content may falsie appear visible when it is closed\n const closedDetails = element.closest('details:not([open])')\n\n if (!closedDetails) {\n return elementIsVisible\n }\n\n if (closedDetails !== element) {\n const summary = element.closest('summary')\n if (summary && summary.parentNode !== closedDetails) {\n return false\n }\n\n if (summary === null) {\n return false\n }\n }\n\n return elementIsVisible\n}\n\nconst isDisabled = element => {\n if (!element || element.nodeType !== Node.ELEMENT_NODE) {\n return true\n }\n\n if (element.classList.contains('disabled')) {\n return true\n }\n\n if (typeof element.disabled !== 'undefined') {\n return element.disabled\n }\n\n return element.hasAttribute('disabled') && element.getAttribute('disabled') !== 'false'\n}\n\nconst findShadowRoot = element => {\n if (!document.documentElement.attachShadow) {\n return null\n }\n\n // Can find the shadow root otherwise it'll return the document\n if (typeof element.getRootNode === 'function') {\n const root = element.getRootNode()\n return root instanceof ShadowRoot ? root : null\n }\n\n if (element instanceof ShadowRoot) {\n return element\n }\n\n // when we don't find a shadow root\n if (!element.parentNode) {\n return null\n }\n\n return findShadowRoot(element.parentNode)\n}\n\nconst noop = () => {}\n\n/**\n * Trick to restart an element's animation\n *\n * @param {HTMLElement} element\n * @return void\n *\n * @see https://www.charistheo.io/blog/2021/02/restart-a-css-animation-with-javascript/#restarting-a-css-animation\n */\nconst reflow = element => {\n element.offsetHeight // eslint-disable-line no-unused-expressions\n}\n\nconst getjQuery = () => {\n if (window.jQuery && !document.body.hasAttribute('data-bs-no-jquery')) {\n return window.jQuery\n }\n\n return null\n}\n\nconst DOMContentLoadedCallbacks = []\n\nconst onDOMContentLoaded = callback => {\n if (document.readyState === 'loading') {\n // add listener on the first call when the document is in loading state\n if (!DOMContentLoadedCallbacks.length) {\n document.addEventListener('DOMContentLoaded', () => {\n for (const callback of DOMContentLoadedCallbacks) {\n callback()\n }\n })\n }\n\n DOMContentLoadedCallbacks.push(callback)\n } else {\n callback()\n }\n}\n\nconst isRTL = () => document.documentElement.dir === 'rtl'\n\nconst defineJQueryPlugin = plugin => {\n onDOMContentLoaded(() => {\n const $ = getjQuery()\n /* istanbul ignore if */\n if ($) {\n const name = plugin.NAME\n const JQUERY_NO_CONFLICT = $.fn[name]\n $.fn[name] = plugin.jQueryInterface\n $.fn[name].Constructor = plugin\n $.fn[name].noConflict = () => {\n $.fn[name] = JQUERY_NO_CONFLICT\n return plugin.jQueryInterface\n }\n }\n })\n}\n\nconst execute = (possibleCallback, args = [], defaultValue = possibleCallback) => {\n return typeof possibleCallback === 'function' ? possibleCallback(...args) : defaultValue\n}\n\nconst executeAfterTransition = (callback, transitionElement, waitForTransition = true) => {\n if (!waitForTransition) {\n execute(callback)\n return\n }\n\n const durationPadding = 5\n const emulatedDuration = getTransitionDurationFromElement(transitionElement) + durationPadding\n\n let called = false\n\n const handler = ({ target }) => {\n if (target !== transitionElement) {\n return\n }\n\n called = true\n transitionElement.removeEventListener(TRANSITION_END, handler)\n execute(callback)\n }\n\n transitionElement.addEventListener(TRANSITION_END, handler)\n setTimeout(() => {\n if (!called) {\n triggerTransitionEnd(transitionElement)\n }\n }, emulatedDuration)\n}\n\n/**\n * Return the previous/next element of a list.\n *\n * @param {array} list The list of elements\n * @param activeElement The active element\n * @param shouldGetNext Choose to get next or previous element\n * @param isCycleAllowed\n * @return {Element|elem} The proper element\n */\nconst getNextActiveElement = (list, activeElement, shouldGetNext, isCycleAllowed) => {\n const listLength = list.length\n let index = list.indexOf(activeElement)\n\n // if the element does not exist in the list return an element\n // depending on the direction and if cycle is allowed\n if (index === -1) {\n return !shouldGetNext && isCycleAllowed ? list[listLength - 1] : list[0]\n }\n\n index += shouldGetNext ? 1 : -1\n\n if (isCycleAllowed) {\n index = (index + listLength) % listLength\n }\n\n return list[Math.max(0, Math.min(index, listLength - 1))]\n}\n\nexport {\n defineJQueryPlugin,\n execute,\n executeAfterTransition,\n findShadowRoot,\n getElement,\n getjQuery,\n getNextActiveElement,\n getTransitionDurationFromElement,\n getUID,\n isDisabled,\n isElement,\n isRTL,\n isVisible,\n noop,\n onDOMContentLoaded,\n parseSelector,\n reflow,\n triggerTransitionEnd,\n toType\n}\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap dom/event-handler.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport { getjQuery } from '../util/index.js'\n\n/**\n * Constants\n */\n\nconst namespaceRegex = /[^.]*(?=\\..*)\\.|.*/\nconst stripNameRegex = /\\..*/\nconst stripUidRegex = /::\\d+$/\nconst eventRegistry = {} // Events storage\nlet uidEvent = 1\nconst customEvents = {\n mouseenter: 'mouseover',\n mouseleave: 'mouseout'\n}\n\nconst nativeEvents = new Set([\n 'click',\n 'dblclick',\n 'mouseup',\n 'mousedown',\n 'contextmenu',\n 'mousewheel',\n 'DOMMouseScroll',\n 'mouseover',\n 'mouseout',\n 'mousemove',\n 'selectstart',\n 'selectend',\n 'keydown',\n 'keypress',\n 'keyup',\n 'orientationchange',\n 'touchstart',\n 'touchmove',\n 'touchend',\n 'touchcancel',\n 'pointerdown',\n 'pointermove',\n 'pointerup',\n 'pointerleave',\n 'pointercancel',\n 'gesturestart',\n 'gesturechange',\n 'gestureend',\n 'focus',\n 'blur',\n 'change',\n 'reset',\n 'select',\n 'submit',\n 'focusin',\n 'focusout',\n 'load',\n 'unload',\n 'beforeunload',\n 'resize',\n 'move',\n 'DOMContentLoaded',\n 'readystatechange',\n 'error',\n 'abort',\n 'scroll'\n])\n\n/**\n * Private methods\n */\n\nfunction makeEventUid(element, uid) {\n return (uid && `${uid}::${uidEvent++}`) || element.uidEvent || uidEvent++\n}\n\nfunction getElementEvents(element) {\n const uid = makeEventUid(element)\n\n element.uidEvent = uid\n eventRegistry[uid] = eventRegistry[uid] || {}\n\n return eventRegistry[uid]\n}\n\nfunction bootstrapHandler(element, fn) {\n return function handler(event) {\n hydrateObj(event, { delegateTarget: element })\n\n if (handler.oneOff) {\n EventHandler.off(element, event.type, fn)\n }\n\n return fn.apply(element, [event])\n }\n}\n\nfunction bootstrapDelegationHandler(element, selector, fn) {\n return function handler(event) {\n const domElements = element.querySelectorAll(selector)\n\n for (let { target } = event; target && target !== this; target = target.parentNode) {\n for (const domElement of domElements) {\n if (domElement !== target) {\n continue\n }\n\n hydrateObj(event, { delegateTarget: target })\n\n if (handler.oneOff) {\n EventHandler.off(element, event.type, selector, fn)\n }\n\n return fn.apply(target, [event])\n }\n }\n }\n}\n\nfunction findHandler(events, callable, delegationSelector = null) {\n return Object.values(events)\n .find(event => event.callable === callable && event.delegationSelector === delegationSelector)\n}\n\nfunction normalizeParameters(originalTypeEvent, handler, delegationFunction) {\n const isDelegated = typeof handler === 'string'\n // TODO: tooltip passes `false` instead of selector, so we need to check\n const callable = isDelegated ? delegationFunction : (handler || delegationFunction)\n let typeEvent = getTypeEvent(originalTypeEvent)\n\n if (!nativeEvents.has(typeEvent)) {\n typeEvent = originalTypeEvent\n }\n\n return [isDelegated, callable, typeEvent]\n}\n\nfunction addHandler(element, originalTypeEvent, handler, delegationFunction, oneOff) {\n if (typeof originalTypeEvent !== 'string' || !element) {\n return\n }\n\n let [isDelegated, callable, typeEvent] = normalizeParameters(originalTypeEvent, handler, delegationFunction)\n\n // in case of mouseenter or mouseleave wrap the handler within a function that checks for its DOM position\n // this prevents the handler from being dispatched the same way as mouseover or mouseout does\n if (originalTypeEvent in customEvents) {\n const wrapFunction = fn => {\n return function (event) {\n if (!event.relatedTarget || (event.relatedTarget !== event.delegateTarget && !event.delegateTarget.contains(event.relatedTarget))) {\n return fn.call(this, event)\n }\n }\n }\n\n callable = wrapFunction(callable)\n }\n\n const events = getElementEvents(element)\n const handlers = events[typeEvent] || (events[typeEvent] = {})\n const previousFunction = findHandler(handlers, callable, isDelegated ? handler : null)\n\n if (previousFunction) {\n previousFunction.oneOff = previousFunction.oneOff && oneOff\n\n return\n }\n\n const uid = makeEventUid(callable, originalTypeEvent.replace(namespaceRegex, ''))\n const fn = isDelegated ?\n bootstrapDelegationHandler(element, handler, callable) :\n bootstrapHandler(element, callable)\n\n fn.delegationSelector = isDelegated ? handler : null\n fn.callable = callable\n fn.oneOff = oneOff\n fn.uidEvent = uid\n handlers[uid] = fn\n\n element.addEventListener(typeEvent, fn, isDelegated)\n}\n\nfunction removeHandler(element, events, typeEvent, handler, delegationSelector) {\n const fn = findHandler(events[typeEvent], handler, delegationSelector)\n\n if (!fn) {\n return\n }\n\n element.removeEventListener(typeEvent, fn, Boolean(delegationSelector))\n delete events[typeEvent][fn.uidEvent]\n}\n\nfunction removeNamespacedHandlers(element, events, typeEvent, namespace) {\n const storeElementEvent = events[typeEvent] || {}\n\n for (const [handlerKey, event] of Object.entries(storeElementEvent)) {\n if (handlerKey.includes(namespace)) {\n removeHandler(element, events, typeEvent, event.callable, event.delegationSelector)\n }\n }\n}\n\nfunction getTypeEvent(event) {\n // allow to get the native events from namespaced events ('click.bs.button' --> 'click')\n event = event.replace(stripNameRegex, '')\n return customEvents[event] || event\n}\n\nconst EventHandler = {\n on(element, event, handler, delegationFunction) {\n addHandler(element, event, handler, delegationFunction, false)\n },\n\n one(element, event, handler, delegationFunction) {\n addHandler(element, event, handler, delegationFunction, true)\n },\n\n off(element, originalTypeEvent, handler, delegationFunction) {\n if (typeof originalTypeEvent !== 'string' || !element) {\n return\n }\n\n const [isDelegated, callable, typeEvent] = normalizeParameters(originalTypeEvent, handler, delegationFunction)\n const inNamespace = typeEvent !== originalTypeEvent\n const events = getElementEvents(element)\n const storeElementEvent = events[typeEvent] || {}\n const isNamespace = originalTypeEvent.startsWith('.')\n\n if (typeof callable !== 'undefined') {\n // Simplest case: handler is passed, remove that listener ONLY.\n if (!Object.keys(storeElementEvent).length) {\n return\n }\n\n removeHandler(element, events, typeEvent, callable, isDelegated ? handler : null)\n return\n }\n\n if (isNamespace) {\n for (const elementEvent of Object.keys(events)) {\n removeNamespacedHandlers(element, events, elementEvent, originalTypeEvent.slice(1))\n }\n }\n\n for (const [keyHandlers, event] of Object.entries(storeElementEvent)) {\n const handlerKey = keyHandlers.replace(stripUidRegex, '')\n\n if (!inNamespace || originalTypeEvent.includes(handlerKey)) {\n removeHandler(element, events, typeEvent, event.callable, event.delegationSelector)\n }\n }\n },\n\n trigger(element, event, args) {\n if (typeof event !== 'string' || !element) {\n return null\n }\n\n const $ = getjQuery()\n const typeEvent = getTypeEvent(event)\n const inNamespace = event !== typeEvent\n\n let jQueryEvent = null\n let bubbles = true\n let nativeDispatch = true\n let defaultPrevented = false\n\n if (inNamespace && $) {\n jQueryEvent = $.Event(event, args)\n\n $(element).trigger(jQueryEvent)\n bubbles = !jQueryEvent.isPropagationStopped()\n nativeDispatch = !jQueryEvent.isImmediatePropagationStopped()\n defaultPrevented = jQueryEvent.isDefaultPrevented()\n }\n\n const evt = hydrateObj(new Event(event, { bubbles, cancelable: true }), args)\n\n if (defaultPrevented) {\n evt.preventDefault()\n }\n\n if (nativeDispatch) {\n element.dispatchEvent(evt)\n }\n\n if (evt.defaultPrevented && jQueryEvent) {\n jQueryEvent.preventDefault()\n }\n\n return evt\n }\n}\n\nfunction hydrateObj(obj, meta = {}) {\n for (const [key, value] of Object.entries(meta)) {\n try {\n obj[key] = value\n } catch {\n Object.defineProperty(obj, key, {\n configurable: true,\n get() {\n return value\n }\n })\n }\n }\n\n return obj\n}\n\nexport default EventHandler\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap dom/manipulator.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nfunction normalizeData(value) {\n if (value === 'true') {\n return true\n }\n\n if (value === 'false') {\n return false\n }\n\n if (value === Number(value).toString()) {\n return Number(value)\n }\n\n if (value === '' || value === 'null') {\n return null\n }\n\n if (typeof value !== 'string') {\n return value\n }\n\n try {\n return JSON.parse(decodeURIComponent(value))\n } catch {\n return value\n }\n}\n\nfunction normalizeDataKey(key) {\n return key.replace(/[A-Z]/g, chr => `-${chr.toLowerCase()}`)\n}\n\nconst Manipulator = {\n setDataAttribute(element, key, value) {\n element.setAttribute(`data-bs-${normalizeDataKey(key)}`, value)\n },\n\n removeDataAttribute(element, key) {\n element.removeAttribute(`data-bs-${normalizeDataKey(key)}`)\n },\n\n getDataAttributes(element) {\n if (!element) {\n return {}\n }\n\n const attributes = {}\n const bsKeys = Object.keys(element.dataset).filter(key => key.startsWith('bs') && !key.startsWith('bsConfig'))\n\n for (const key of bsKeys) {\n let pureKey = key.replace(/^bs/, '')\n pureKey = pureKey.charAt(0).toLowerCase() + pureKey.slice(1, pureKey.length)\n attributes[pureKey] = normalizeData(element.dataset[key])\n }\n\n return attributes\n },\n\n getDataAttribute(element, key) {\n return normalizeData(element.getAttribute(`data-bs-${normalizeDataKey(key)}`))\n }\n}\n\nexport default Manipulator\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap util/config.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport Manipulator from '../dom/manipulator.js'\nimport { isElement, toType } from './index.js'\n\n/**\n * Class definition\n */\n\nclass Config {\n // Getters\n static get Default() {\n return {}\n }\n\n static get DefaultType() {\n return {}\n }\n\n static get NAME() {\n throw new Error('You have to implement the static method \"NAME\", for each component!')\n }\n\n _getConfig(config) {\n config = this._mergeConfigObj(config)\n config = this._configAfterMerge(config)\n this._typeCheckConfig(config)\n return config\n }\n\n _configAfterMerge(config) {\n return config\n }\n\n _mergeConfigObj(config, element) {\n const jsonConfig = isElement(element) ? Manipulator.getDataAttribute(element, 'config') : {} // try to parse\n\n return {\n ...this.constructor.Default,\n ...(typeof jsonConfig === 'object' ? jsonConfig : {}),\n ...(isElement(element) ? Manipulator.getDataAttributes(element) : {}),\n ...(typeof config === 'object' ? config : {})\n }\n }\n\n _typeCheckConfig(config, configTypes = this.constructor.DefaultType) {\n for (const [property, expectedTypes] of Object.entries(configTypes)) {\n const value = config[property]\n const valueType = isElement(value) ? 'element' : toType(value)\n\n if (!new RegExp(expectedTypes).test(valueType)) {\n throw new TypeError(\n `${this.constructor.NAME.toUpperCase()}: Option \"${property}\" provided type \"${valueType}\" but expected type \"${expectedTypes}\".`\n )\n }\n }\n }\n}\n\nexport default Config\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap base-component.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport Data from './dom/data.js'\nimport EventHandler from './dom/event-handler.js'\nimport Config from './util/config.js'\nimport { executeAfterTransition, getElement } from './util/index.js'\n\n/**\n * Constants\n */\n\nconst VERSION = '5.3.1'\n\n/**\n * Class definition\n */\n\nclass BaseComponent extends Config {\n constructor(element, config) {\n super()\n\n element = getElement(element)\n if (!element) {\n return\n }\n\n this._element = element\n this._config = this._getConfig(config)\n\n Data.set(this._element, this.constructor.DATA_KEY, this)\n }\n\n // Public\n dispose() {\n Data.remove(this._element, this.constructor.DATA_KEY)\n EventHandler.off(this._element, this.constructor.EVENT_KEY)\n\n for (const propertyName of Object.getOwnPropertyNames(this)) {\n this[propertyName] = null\n }\n }\n\n _queueCallback(callback, element, isAnimated = true) {\n executeAfterTransition(callback, element, isAnimated)\n }\n\n _getConfig(config) {\n config = this._mergeConfigObj(config, this._element)\n config = this._configAfterMerge(config)\n this._typeCheckConfig(config)\n return config\n }\n\n // Static\n static getInstance(element) {\n return Data.get(getElement(element), this.DATA_KEY)\n }\n\n static getOrCreateInstance(element, config = {}) {\n return this.getInstance(element) || new this(element, typeof config === 'object' ? config : null)\n }\n\n static get VERSION() {\n return VERSION\n }\n\n static get DATA_KEY() {\n return `bs.${this.NAME}`\n }\n\n static get EVENT_KEY() {\n return `.${this.DATA_KEY}`\n }\n\n static eventName(name) {\n return `${name}${this.EVENT_KEY}`\n }\n}\n\nexport default BaseComponent\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap dom/selector-engine.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport { isDisabled, isVisible, parseSelector } from '../util/index.js'\n\nconst getSelector = element => {\n let selector = element.getAttribute('data-bs-target')\n\n if (!selector || selector === '#') {\n let hrefAttribute = element.getAttribute('href')\n\n // The only valid content that could double as a selector are IDs or classes,\n // so everything starting with `#` or `.`. If a \"real\" URL is used as the selector,\n // `document.querySelector` will rightfully complain it is invalid.\n // See https://github.com/twbs/bootstrap/issues/32273\n if (!hrefAttribute || (!hrefAttribute.includes('#') && !hrefAttribute.startsWith('.'))) {\n return null\n }\n\n // Just in case some CMS puts out a full URL with the anchor appended\n if (hrefAttribute.includes('#') && !hrefAttribute.startsWith('#')) {\n hrefAttribute = `#${hrefAttribute.split('#')[1]}`\n }\n\n selector = hrefAttribute && hrefAttribute !== '#' ? hrefAttribute.trim() : null\n }\n\n return parseSelector(selector)\n}\n\nconst SelectorEngine = {\n find(selector, element = document.documentElement) {\n return [].concat(...Element.prototype.querySelectorAll.call(element, selector))\n },\n\n findOne(selector, element = document.documentElement) {\n return Element.prototype.querySelector.call(element, selector)\n },\n\n children(element, selector) {\n return [].concat(...element.children).filter(child => child.matches(selector))\n },\n\n parents(element, selector) {\n const parents = []\n let ancestor = element.parentNode.closest(selector)\n\n while (ancestor) {\n parents.push(ancestor)\n ancestor = ancestor.parentNode.closest(selector)\n }\n\n return parents\n },\n\n prev(element, selector) {\n let previous = element.previousElementSibling\n\n while (previous) {\n if (previous.matches(selector)) {\n return [previous]\n }\n\n previous = previous.previousElementSibling\n }\n\n return []\n },\n // TODO: this is now unused; remove later along with prev()\n next(element, selector) {\n let next = element.nextElementSibling\n\n while (next) {\n if (next.matches(selector)) {\n return [next]\n }\n\n next = next.nextElementSibling\n }\n\n return []\n },\n\n focusableChildren(element) {\n const focusables = [\n 'a',\n 'button',\n 'input',\n 'textarea',\n 'select',\n 'details',\n '[tabindex]',\n '[contenteditable=\"true\"]'\n ].map(selector => `${selector}:not([tabindex^=\"-\"])`).join(',')\n\n return this.find(focusables, element).filter(el => !isDisabled(el) && isVisible(el))\n },\n\n getSelectorFromElement(element) {\n const selector = getSelector(element)\n\n if (selector) {\n return SelectorEngine.findOne(selector) ? selector : null\n }\n\n return null\n },\n\n getElementFromSelector(element) {\n const selector = getSelector(element)\n\n return selector ? SelectorEngine.findOne(selector) : null\n },\n\n getMultipleElementsFromSelector(element) {\n const selector = getSelector(element)\n\n return selector ? SelectorEngine.find(selector) : []\n }\n}\n\nexport default SelectorEngine\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap util/component-functions.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport EventHandler from '../dom/event-handler.js'\nimport SelectorEngine from '../dom/selector-engine.js'\nimport { isDisabled } from './index.js'\n\nconst enableDismissTrigger = (component, method = 'hide') => {\n const clickEvent = `click.dismiss${component.EVENT_KEY}`\n const name = component.NAME\n\n EventHandler.on(document, clickEvent, `[data-bs-dismiss=\"${name}\"]`, function (event) {\n if (['A', 'AREA'].includes(this.tagName)) {\n event.preventDefault()\n }\n\n if (isDisabled(this)) {\n return\n }\n\n const target = SelectorEngine.getElementFromSelector(this) || this.closest(`.${name}`)\n const instance = component.getOrCreateInstance(target)\n\n // Method argument is left, for Alert and only, as it doesn't implement the 'hide' method\n instance[method]()\n })\n}\n\nexport {\n enableDismissTrigger\n}\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap alert.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport BaseComponent from './base-component.js'\nimport EventHandler from './dom/event-handler.js'\nimport { enableDismissTrigger } from './util/component-functions.js'\nimport { defineJQueryPlugin } from './util/index.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'alert'\nconst DATA_KEY = 'bs.alert'\nconst EVENT_KEY = `.${DATA_KEY}`\n\nconst EVENT_CLOSE = `close${EVENT_KEY}`\nconst EVENT_CLOSED = `closed${EVENT_KEY}`\nconst CLASS_NAME_FADE = 'fade'\nconst CLASS_NAME_SHOW = 'show'\n\n/**\n * Class definition\n */\n\nclass Alert extends BaseComponent {\n // Getters\n static get NAME() {\n return NAME\n }\n\n // Public\n close() {\n const closeEvent = EventHandler.trigger(this._element, EVENT_CLOSE)\n\n if (closeEvent.defaultPrevented) {\n return\n }\n\n this._element.classList.remove(CLASS_NAME_SHOW)\n\n const isAnimated = this._element.classList.contains(CLASS_NAME_FADE)\n this._queueCallback(() => this._destroyElement(), this._element, isAnimated)\n }\n\n // Private\n _destroyElement() {\n this._element.remove()\n EventHandler.trigger(this._element, EVENT_CLOSED)\n this.dispose()\n }\n\n // Static\n static jQueryInterface(config) {\n return this.each(function () {\n const data = Alert.getOrCreateInstance(this)\n\n if (typeof config !== 'string') {\n return\n }\n\n if (data[config] === undefined || config.startsWith('_') || config === 'constructor') {\n throw new TypeError(`No method named \"${config}\"`)\n }\n\n data[config](this)\n })\n }\n}\n\n/**\n * Data API implementation\n */\n\nenableDismissTrigger(Alert, 'close')\n\n/**\n * jQuery\n */\n\ndefineJQueryPlugin(Alert)\n\nexport default Alert\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap button.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport BaseComponent from './base-component.js'\nimport EventHandler from './dom/event-handler.js'\nimport { defineJQueryPlugin } from './util/index.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'button'\nconst DATA_KEY = 'bs.button'\nconst EVENT_KEY = `.${DATA_KEY}`\nconst DATA_API_KEY = '.data-api'\n\nconst CLASS_NAME_ACTIVE = 'active'\nconst SELECTOR_DATA_TOGGLE = '[data-bs-toggle=\"button\"]'\nconst EVENT_CLICK_DATA_API = `click${EVENT_KEY}${DATA_API_KEY}`\n\n/**\n * Class definition\n */\n\nclass Button extends BaseComponent {\n // Getters\n static get NAME() {\n return NAME\n }\n\n // Public\n toggle() {\n // Toggle class and sync the `aria-pressed` attribute with the return value of the `.toggle()` method\n this._element.setAttribute('aria-pressed', this._element.classList.toggle(CLASS_NAME_ACTIVE))\n }\n\n // Static\n static jQueryInterface(config) {\n return this.each(function () {\n const data = Button.getOrCreateInstance(this)\n\n if (config === 'toggle') {\n data[config]()\n }\n })\n }\n}\n\n/**\n * Data API implementation\n */\n\nEventHandler.on(document, EVENT_CLICK_DATA_API, SELECTOR_DATA_TOGGLE, event => {\n event.preventDefault()\n\n const button = event.target.closest(SELECTOR_DATA_TOGGLE)\n const data = Button.getOrCreateInstance(button)\n\n data.toggle()\n})\n\n/**\n * jQuery\n */\n\ndefineJQueryPlugin(Button)\n\nexport default Button\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap util/swipe.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport EventHandler from '../dom/event-handler.js'\nimport Config from './config.js'\nimport { execute } from './index.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'swipe'\nconst EVENT_KEY = '.bs.swipe'\nconst EVENT_TOUCHSTART = `touchstart${EVENT_KEY}`\nconst EVENT_TOUCHMOVE = `touchmove${EVENT_KEY}`\nconst EVENT_TOUCHEND = `touchend${EVENT_KEY}`\nconst EVENT_POINTERDOWN = `pointerdown${EVENT_KEY}`\nconst EVENT_POINTERUP = `pointerup${EVENT_KEY}`\nconst POINTER_TYPE_TOUCH = 'touch'\nconst POINTER_TYPE_PEN = 'pen'\nconst CLASS_NAME_POINTER_EVENT = 'pointer-event'\nconst SWIPE_THRESHOLD = 40\n\nconst Default = {\n endCallback: null,\n leftCallback: null,\n rightCallback: null\n}\n\nconst DefaultType = {\n endCallback: '(function|null)',\n leftCallback: '(function|null)',\n rightCallback: '(function|null)'\n}\n\n/**\n * Class definition\n */\n\nclass Swipe extends Config {\n constructor(element, config) {\n super()\n this._element = element\n\n if (!element || !Swipe.isSupported()) {\n return\n }\n\n this._config = this._getConfig(config)\n this._deltaX = 0\n this._supportPointerEvents = Boolean(window.PointerEvent)\n this._initEvents()\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n dispose() {\n EventHandler.off(this._element, EVENT_KEY)\n }\n\n // Private\n _start(event) {\n if (!this._supportPointerEvents) {\n this._deltaX = event.touches[0].clientX\n\n return\n }\n\n if (this._eventIsPointerPenTouch(event)) {\n this._deltaX = event.clientX\n }\n }\n\n _end(event) {\n if (this._eventIsPointerPenTouch(event)) {\n this._deltaX = event.clientX - this._deltaX\n }\n\n this._handleSwipe()\n execute(this._config.endCallback)\n }\n\n _move(event) {\n this._deltaX = event.touches && event.touches.length > 1 ?\n 0 :\n event.touches[0].clientX - this._deltaX\n }\n\n _handleSwipe() {\n const absDeltaX = Math.abs(this._deltaX)\n\n if (absDeltaX <= SWIPE_THRESHOLD) {\n return\n }\n\n const direction = absDeltaX / this._deltaX\n\n this._deltaX = 0\n\n if (!direction) {\n return\n }\n\n execute(direction > 0 ? this._config.rightCallback : this._config.leftCallback)\n }\n\n _initEvents() {\n if (this._supportPointerEvents) {\n EventHandler.on(this._element, EVENT_POINTERDOWN, event => this._start(event))\n EventHandler.on(this._element, EVENT_POINTERUP, event => this._end(event))\n\n this._element.classList.add(CLASS_NAME_POINTER_EVENT)\n } else {\n EventHandler.on(this._element, EVENT_TOUCHSTART, event => this._start(event))\n EventHandler.on(this._element, EVENT_TOUCHMOVE, event => this._move(event))\n EventHandler.on(this._element, EVENT_TOUCHEND, event => this._end(event))\n }\n }\n\n _eventIsPointerPenTouch(event) {\n return this._supportPointerEvents && (event.pointerType === POINTER_TYPE_PEN || event.pointerType === POINTER_TYPE_TOUCH)\n }\n\n // Static\n static isSupported() {\n return 'ontouchstart' in document.documentElement || navigator.maxTouchPoints > 0\n }\n}\n\nexport default Swipe\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap carousel.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport BaseComponent from './base-component.js'\nimport EventHandler from './dom/event-handler.js'\nimport Manipulator from './dom/manipulator.js'\nimport SelectorEngine from './dom/selector-engine.js'\nimport {\n defineJQueryPlugin,\n getNextActiveElement,\n isRTL,\n isVisible,\n reflow,\n triggerTransitionEnd\n} from './util/index.js'\nimport Swipe from './util/swipe.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'carousel'\nconst DATA_KEY = 'bs.carousel'\nconst EVENT_KEY = `.${DATA_KEY}`\nconst DATA_API_KEY = '.data-api'\n\nconst ARROW_LEFT_KEY = 'ArrowLeft'\nconst ARROW_RIGHT_KEY = 'ArrowRight'\nconst TOUCHEVENT_COMPAT_WAIT = 500 // Time for mouse compat events to fire after touch\n\nconst ORDER_NEXT = 'next'\nconst ORDER_PREV = 'prev'\nconst DIRECTION_LEFT = 'left'\nconst DIRECTION_RIGHT = 'right'\n\nconst EVENT_SLIDE = `slide${EVENT_KEY}`\nconst EVENT_SLID = `slid${EVENT_KEY}`\nconst EVENT_KEYDOWN = `keydown${EVENT_KEY}`\nconst EVENT_MOUSEENTER = `mouseenter${EVENT_KEY}`\nconst EVENT_MOUSELEAVE = `mouseleave${EVENT_KEY}`\nconst EVENT_DRAG_START = `dragstart${EVENT_KEY}`\nconst EVENT_LOAD_DATA_API = `load${EVENT_KEY}${DATA_API_KEY}`\nconst EVENT_CLICK_DATA_API = `click${EVENT_KEY}${DATA_API_KEY}`\n\nconst CLASS_NAME_CAROUSEL = 'carousel'\nconst CLASS_NAME_ACTIVE = 'active'\nconst CLASS_NAME_SLIDE = 'slide'\nconst CLASS_NAME_END = 'carousel-item-end'\nconst CLASS_NAME_START = 'carousel-item-start'\nconst CLASS_NAME_NEXT = 'carousel-item-next'\nconst CLASS_NAME_PREV = 'carousel-item-prev'\n\nconst SELECTOR_ACTIVE = '.active'\nconst SELECTOR_ITEM = '.carousel-item'\nconst SELECTOR_ACTIVE_ITEM = SELECTOR_ACTIVE + SELECTOR_ITEM\nconst SELECTOR_ITEM_IMG = '.carousel-item img'\nconst SELECTOR_INDICATORS = '.carousel-indicators'\nconst SELECTOR_DATA_SLIDE = '[data-bs-slide], [data-bs-slide-to]'\nconst SELECTOR_DATA_RIDE = '[data-bs-ride=\"carousel\"]'\n\nconst KEY_TO_DIRECTION = {\n [ARROW_LEFT_KEY]: DIRECTION_RIGHT,\n [ARROW_RIGHT_KEY]: DIRECTION_LEFT\n}\n\nconst Default = {\n interval: 5000,\n keyboard: true,\n pause: 'hover',\n ride: false,\n touch: true,\n wrap: true\n}\n\nconst DefaultType = {\n interval: '(number|boolean)', // TODO:v6 remove boolean support\n keyboard: 'boolean',\n pause: '(string|boolean)',\n ride: '(boolean|string)',\n touch: 'boolean',\n wrap: 'boolean'\n}\n\n/**\n * Class definition\n */\n\nclass Carousel extends BaseComponent {\n constructor(element, config) {\n super(element, config)\n\n this._interval = null\n this._activeElement = null\n this._isSliding = false\n this.touchTimeout = null\n this._swipeHelper = null\n\n this._indicatorsElement = SelectorEngine.findOne(SELECTOR_INDICATORS, this._element)\n this._addEventListeners()\n\n if (this._config.ride === CLASS_NAME_CAROUSEL) {\n this.cycle()\n }\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n next() {\n this._slide(ORDER_NEXT)\n }\n\n nextWhenVisible() {\n // FIXME TODO use `document.visibilityState`\n // Don't call next when the page isn't visible\n // or the carousel or its parent isn't visible\n if (!document.hidden && isVisible(this._element)) {\n this.next()\n }\n }\n\n prev() {\n this._slide(ORDER_PREV)\n }\n\n pause() {\n if (this._isSliding) {\n triggerTransitionEnd(this._element)\n }\n\n this._clearInterval()\n }\n\n cycle() {\n this._clearInterval()\n this._updateInterval()\n\n this._interval = setInterval(() => this.nextWhenVisible(), this._config.interval)\n }\n\n _maybeEnableCycle() {\n if (!this._config.ride) {\n return\n }\n\n if (this._isSliding) {\n EventHandler.one(this._element, EVENT_SLID, () => this.cycle())\n return\n }\n\n this.cycle()\n }\n\n to(index) {\n const items = this._getItems()\n if (index > items.length - 1 || index < 0) {\n return\n }\n\n if (this._isSliding) {\n EventHandler.one(this._element, EVENT_SLID, () => this.to(index))\n return\n }\n\n const activeIndex = this._getItemIndex(this._getActive())\n if (activeIndex === index) {\n return\n }\n\n const order = index > activeIndex ? ORDER_NEXT : ORDER_PREV\n\n this._slide(order, items[index])\n }\n\n dispose() {\n if (this._swipeHelper) {\n this._swipeHelper.dispose()\n }\n\n super.dispose()\n }\n\n // Private\n _configAfterMerge(config) {\n config.defaultInterval = config.interval\n return config\n }\n\n _addEventListeners() {\n if (this._config.keyboard) {\n EventHandler.on(this._element, EVENT_KEYDOWN, event => this._keydown(event))\n }\n\n if (this._config.pause === 'hover') {\n EventHandler.on(this._element, EVENT_MOUSEENTER, () => this.pause())\n EventHandler.on(this._element, EVENT_MOUSELEAVE, () => this._maybeEnableCycle())\n }\n\n if (this._config.touch && Swipe.isSupported()) {\n this._addTouchEventListeners()\n }\n }\n\n _addTouchEventListeners() {\n for (const img of SelectorEngine.find(SELECTOR_ITEM_IMG, this._element)) {\n EventHandler.on(img, EVENT_DRAG_START, event => event.preventDefault())\n }\n\n const endCallBack = () => {\n if (this._config.pause !== 'hover') {\n return\n }\n\n // If it's a touch-enabled device, mouseenter/leave are fired as\n // part of the mouse compatibility events on first tap - the carousel\n // would stop cycling until user tapped out of it;\n // here, we listen for touchend, explicitly pause the carousel\n // (as if it's the second time we tap on it, mouseenter compat event\n // is NOT fired) and after a timeout (to allow for mouse compatibility\n // events to fire) we explicitly restart cycling\n\n this.pause()\n if (this.touchTimeout) {\n clearTimeout(this.touchTimeout)\n }\n\n this.touchTimeout = setTimeout(() => this._maybeEnableCycle(), TOUCHEVENT_COMPAT_WAIT + this._config.interval)\n }\n\n const swipeConfig = {\n leftCallback: () => this._slide(this._directionToOrder(DIRECTION_LEFT)),\n rightCallback: () => this._slide(this._directionToOrder(DIRECTION_RIGHT)),\n endCallback: endCallBack\n }\n\n this._swipeHelper = new Swipe(this._element, swipeConfig)\n }\n\n _keydown(event) {\n if (/input|textarea/i.test(event.target.tagName)) {\n return\n }\n\n const direction = KEY_TO_DIRECTION[event.key]\n if (direction) {\n event.preventDefault()\n this._slide(this._directionToOrder(direction))\n }\n }\n\n _getItemIndex(element) {\n return this._getItems().indexOf(element)\n }\n\n _setActiveIndicatorElement(index) {\n if (!this._indicatorsElement) {\n return\n }\n\n const activeIndicator = SelectorEngine.findOne(SELECTOR_ACTIVE, this._indicatorsElement)\n\n activeIndicator.classList.remove(CLASS_NAME_ACTIVE)\n activeIndicator.removeAttribute('aria-current')\n\n const newActiveIndicator = SelectorEngine.findOne(`[data-bs-slide-to=\"${index}\"]`, this._indicatorsElement)\n\n if (newActiveIndicator) {\n newActiveIndicator.classList.add(CLASS_NAME_ACTIVE)\n newActiveIndicator.setAttribute('aria-current', 'true')\n }\n }\n\n _updateInterval() {\n const element = this._activeElement || this._getActive()\n\n if (!element) {\n return\n }\n\n const elementInterval = Number.parseInt(element.getAttribute('data-bs-interval'), 10)\n\n this._config.interval = elementInterval || this._config.defaultInterval\n }\n\n _slide(order, element = null) {\n if (this._isSliding) {\n return\n }\n\n const activeElement = this._getActive()\n const isNext = order === ORDER_NEXT\n const nextElement = element || getNextActiveElement(this._getItems(), activeElement, isNext, this._config.wrap)\n\n if (nextElement === activeElement) {\n return\n }\n\n const nextElementIndex = this._getItemIndex(nextElement)\n\n const triggerEvent = eventName => {\n return EventHandler.trigger(this._element, eventName, {\n relatedTarget: nextElement,\n direction: this._orderToDirection(order),\n from: this._getItemIndex(activeElement),\n to: nextElementIndex\n })\n }\n\n const slideEvent = triggerEvent(EVENT_SLIDE)\n\n if (slideEvent.defaultPrevented) {\n return\n }\n\n if (!activeElement || !nextElement) {\n // Some weirdness is happening, so we bail\n // TODO: change tests that use empty divs to avoid this check\n return\n }\n\n const isCycling = Boolean(this._interval)\n this.pause()\n\n this._isSliding = true\n\n this._setActiveIndicatorElement(nextElementIndex)\n this._activeElement = nextElement\n\n const directionalClassName = isNext ? CLASS_NAME_START : CLASS_NAME_END\n const orderClassName = isNext ? CLASS_NAME_NEXT : CLASS_NAME_PREV\n\n nextElement.classList.add(orderClassName)\n\n reflow(nextElement)\n\n activeElement.classList.add(directionalClassName)\n nextElement.classList.add(directionalClassName)\n\n const completeCallBack = () => {\n nextElement.classList.remove(directionalClassName, orderClassName)\n nextElement.classList.add(CLASS_NAME_ACTIVE)\n\n activeElement.classList.remove(CLASS_NAME_ACTIVE, orderClassName, directionalClassName)\n\n this._isSliding = false\n\n triggerEvent(EVENT_SLID)\n }\n\n this._queueCallback(completeCallBack, activeElement, this._isAnimated())\n\n if (isCycling) {\n this.cycle()\n }\n }\n\n _isAnimated() {\n return this._element.classList.contains(CLASS_NAME_SLIDE)\n }\n\n _getActive() {\n return SelectorEngine.findOne(SELECTOR_ACTIVE_ITEM, this._element)\n }\n\n _getItems() {\n return SelectorEngine.find(SELECTOR_ITEM, this._element)\n }\n\n _clearInterval() {\n if (this._interval) {\n clearInterval(this._interval)\n this._interval = null\n }\n }\n\n _directionToOrder(direction) {\n if (isRTL()) {\n return direction === DIRECTION_LEFT ? ORDER_PREV : ORDER_NEXT\n }\n\n return direction === DIRECTION_LEFT ? ORDER_NEXT : ORDER_PREV\n }\n\n _orderToDirection(order) {\n if (isRTL()) {\n return order === ORDER_PREV ? DIRECTION_LEFT : DIRECTION_RIGHT\n }\n\n return order === ORDER_PREV ? DIRECTION_RIGHT : DIRECTION_LEFT\n }\n\n // Static\n static jQueryInterface(config) {\n return this.each(function () {\n const data = Carousel.getOrCreateInstance(this, config)\n\n if (typeof config === 'number') {\n data.to(config)\n return\n }\n\n if (typeof config === 'string') {\n if (data[config] === undefined || config.startsWith('_') || config === 'constructor') {\n throw new TypeError(`No method named \"${config}\"`)\n }\n\n data[config]()\n }\n })\n }\n}\n\n/**\n * Data API implementation\n */\n\nEventHandler.on(document, EVENT_CLICK_DATA_API, SELECTOR_DATA_SLIDE, function (event) {\n const target = SelectorEngine.getElementFromSelector(this)\n\n if (!target || !target.classList.contains(CLASS_NAME_CAROUSEL)) {\n return\n }\n\n event.preventDefault()\n\n const carousel = Carousel.getOrCreateInstance(target)\n const slideIndex = this.getAttribute('data-bs-slide-to')\n\n if (slideIndex) {\n carousel.to(slideIndex)\n carousel._maybeEnableCycle()\n return\n }\n\n if (Manipulator.getDataAttribute(this, 'slide') === 'next') {\n carousel.next()\n carousel._maybeEnableCycle()\n return\n }\n\n carousel.prev()\n carousel._maybeEnableCycle()\n})\n\nEventHandler.on(window, EVENT_LOAD_DATA_API, () => {\n const carousels = SelectorEngine.find(SELECTOR_DATA_RIDE)\n\n for (const carousel of carousels) {\n Carousel.getOrCreateInstance(carousel)\n }\n})\n\n/**\n * jQuery\n */\n\ndefineJQueryPlugin(Carousel)\n\nexport default Carousel\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap collapse.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport BaseComponent from './base-component.js'\nimport EventHandler from './dom/event-handler.js'\nimport SelectorEngine from './dom/selector-engine.js'\nimport {\n defineJQueryPlugin,\n getElement,\n reflow\n} from './util/index.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'collapse'\nconst DATA_KEY = 'bs.collapse'\nconst EVENT_KEY = `.${DATA_KEY}`\nconst DATA_API_KEY = '.data-api'\n\nconst EVENT_SHOW = `show${EVENT_KEY}`\nconst EVENT_SHOWN = `shown${EVENT_KEY}`\nconst EVENT_HIDE = `hide${EVENT_KEY}`\nconst EVENT_HIDDEN = `hidden${EVENT_KEY}`\nconst EVENT_CLICK_DATA_API = `click${EVENT_KEY}${DATA_API_KEY}`\n\nconst CLASS_NAME_SHOW = 'show'\nconst CLASS_NAME_COLLAPSE = 'collapse'\nconst CLASS_NAME_COLLAPSING = 'collapsing'\nconst CLASS_NAME_COLLAPSED = 'collapsed'\nconst CLASS_NAME_DEEPER_CHILDREN = `:scope .${CLASS_NAME_COLLAPSE} .${CLASS_NAME_COLLAPSE}`\nconst CLASS_NAME_HORIZONTAL = 'collapse-horizontal'\n\nconst WIDTH = 'width'\nconst HEIGHT = 'height'\n\nconst SELECTOR_ACTIVES = '.collapse.show, .collapse.collapsing'\nconst SELECTOR_DATA_TOGGLE = '[data-bs-toggle=\"collapse\"]'\n\nconst Default = {\n parent: null,\n toggle: true\n}\n\nconst DefaultType = {\n parent: '(null|element)',\n toggle: 'boolean'\n}\n\n/**\n * Class definition\n */\n\nclass Collapse extends BaseComponent {\n constructor(element, config) {\n super(element, config)\n\n this._isTransitioning = false\n this._triggerArray = []\n\n const toggleList = SelectorEngine.find(SELECTOR_DATA_TOGGLE)\n\n for (const elem of toggleList) {\n const selector = SelectorEngine.getSelectorFromElement(elem)\n const filterElement = SelectorEngine.find(selector)\n .filter(foundElement => foundElement === this._element)\n\n if (selector !== null && filterElement.length) {\n this._triggerArray.push(elem)\n }\n }\n\n this._initializeChildren()\n\n if (!this._config.parent) {\n this._addAriaAndCollapsedClass(this._triggerArray, this._isShown())\n }\n\n if (this._config.toggle) {\n this.toggle()\n }\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n toggle() {\n if (this._isShown()) {\n this.hide()\n } else {\n this.show()\n }\n }\n\n show() {\n if (this._isTransitioning || this._isShown()) {\n return\n }\n\n let activeChildren = []\n\n // find active children\n if (this._config.parent) {\n activeChildren = this._getFirstLevelChildren(SELECTOR_ACTIVES)\n .filter(element => element !== this._element)\n .map(element => Collapse.getOrCreateInstance(element, { toggle: false }))\n }\n\n if (activeChildren.length && activeChildren[0]._isTransitioning) {\n return\n }\n\n const startEvent = EventHandler.trigger(this._element, EVENT_SHOW)\n if (startEvent.defaultPrevented) {\n return\n }\n\n for (const activeInstance of activeChildren) {\n activeInstance.hide()\n }\n\n const dimension = this._getDimension()\n\n this._element.classList.remove(CLASS_NAME_COLLAPSE)\n this._element.classList.add(CLASS_NAME_COLLAPSING)\n\n this._element.style[dimension] = 0\n\n this._addAriaAndCollapsedClass(this._triggerArray, true)\n this._isTransitioning = true\n\n const complete = () => {\n this._isTransitioning = false\n\n this._element.classList.remove(CLASS_NAME_COLLAPSING)\n this._element.classList.add(CLASS_NAME_COLLAPSE, CLASS_NAME_SHOW)\n\n this._element.style[dimension] = ''\n\n EventHandler.trigger(this._element, EVENT_SHOWN)\n }\n\n const capitalizedDimension = dimension[0].toUpperCase() + dimension.slice(1)\n const scrollSize = `scroll${capitalizedDimension}`\n\n this._queueCallback(complete, this._element, true)\n this._element.style[dimension] = `${this._element[scrollSize]}px`\n }\n\n hide() {\n if (this._isTransitioning || !this._isShown()) {\n return\n }\n\n const startEvent = EventHandler.trigger(this._element, EVENT_HIDE)\n if (startEvent.defaultPrevented) {\n return\n }\n\n const dimension = this._getDimension()\n\n this._element.style[dimension] = `${this._element.getBoundingClientRect()[dimension]}px`\n\n reflow(this._element)\n\n this._element.classList.add(CLASS_NAME_COLLAPSING)\n this._element.classList.remove(CLASS_NAME_COLLAPSE, CLASS_NAME_SHOW)\n\n for (const trigger of this._triggerArray) {\n const element = SelectorEngine.getElementFromSelector(trigger)\n\n if (element && !this._isShown(element)) {\n this._addAriaAndCollapsedClass([trigger], false)\n }\n }\n\n this._isTransitioning = true\n\n const complete = () => {\n this._isTransitioning = false\n this._element.classList.remove(CLASS_NAME_COLLAPSING)\n this._element.classList.add(CLASS_NAME_COLLAPSE)\n EventHandler.trigger(this._element, EVENT_HIDDEN)\n }\n\n this._element.style[dimension] = ''\n\n this._queueCallback(complete, this._element, true)\n }\n\n _isShown(element = this._element) {\n return element.classList.contains(CLASS_NAME_SHOW)\n }\n\n // Private\n _configAfterMerge(config) {\n config.toggle = Boolean(config.toggle) // Coerce string values\n config.parent = getElement(config.parent)\n return config\n }\n\n _getDimension() {\n return this._element.classList.contains(CLASS_NAME_HORIZONTAL) ? WIDTH : HEIGHT\n }\n\n _initializeChildren() {\n if (!this._config.parent) {\n return\n }\n\n const children = this._getFirstLevelChildren(SELECTOR_DATA_TOGGLE)\n\n for (const element of children) {\n const selected = SelectorEngine.getElementFromSelector(element)\n\n if (selected) {\n this._addAriaAndCollapsedClass([element], this._isShown(selected))\n }\n }\n }\n\n _getFirstLevelChildren(selector) {\n const children = SelectorEngine.find(CLASS_NAME_DEEPER_CHILDREN, this._config.parent)\n // remove children if greater depth\n return SelectorEngine.find(selector, this._config.parent).filter(element => !children.includes(element))\n }\n\n _addAriaAndCollapsedClass(triggerArray, isOpen) {\n if (!triggerArray.length) {\n return\n }\n\n for (const element of triggerArray) {\n element.classList.toggle(CLASS_NAME_COLLAPSED, !isOpen)\n element.setAttribute('aria-expanded', isOpen)\n }\n }\n\n // Static\n static jQueryInterface(config) {\n const _config = {}\n if (typeof config === 'string' && /show|hide/.test(config)) {\n _config.toggle = false\n }\n\n return this.each(function () {\n const data = Collapse.getOrCreateInstance(this, _config)\n\n if (typeof config === 'string') {\n if (typeof data[config] === 'undefined') {\n throw new TypeError(`No method named \"${config}\"`)\n }\n\n data[config]()\n }\n })\n }\n}\n\n/**\n * Data API implementation\n */\n\nEventHandler.on(document, EVENT_CLICK_DATA_API, SELECTOR_DATA_TOGGLE, function (event) {\n // preventDefault only for elements (which change the URL) not inside the collapsible element\n if (event.target.tagName === 'A' || (event.delegateTarget && event.delegateTarget.tagName === 'A')) {\n event.preventDefault()\n }\n\n for (const element of SelectorEngine.getMultipleElementsFromSelector(this)) {\n Collapse.getOrCreateInstance(element, { toggle: false }).toggle()\n }\n})\n\n/**\n * jQuery\n */\n\ndefineJQueryPlugin(Collapse)\n\nexport default Collapse\n","export var top = 'top';\nexport var bottom = 'bottom';\nexport var right = 'right';\nexport var left = 'left';\nexport var auto = 'auto';\nexport var basePlacements = [top, bottom, right, left];\nexport var start = 'start';\nexport var end = 'end';\nexport var clippingParents = 'clippingParents';\nexport var viewport = 'viewport';\nexport var popper = 'popper';\nexport var reference = 'reference';\nexport var variationPlacements = /*#__PURE__*/basePlacements.reduce(function (acc, placement) {\n return acc.concat([placement + \"-\" + start, placement + \"-\" + end]);\n}, []);\nexport var placements = /*#__PURE__*/[].concat(basePlacements, [auto]).reduce(function (acc, placement) {\n return acc.concat([placement, placement + \"-\" + start, placement + \"-\" + end]);\n}, []); // modifiers that need to read the DOM\n\nexport var beforeRead = 'beforeRead';\nexport var read = 'read';\nexport var afterRead = 'afterRead'; // pure-logic modifiers\n\nexport var beforeMain = 'beforeMain';\nexport var main = 'main';\nexport var afterMain = 'afterMain'; // modifier with the purpose to write to the DOM (or write into a framework state)\n\nexport var beforeWrite = 'beforeWrite';\nexport var write = 'write';\nexport var afterWrite = 'afterWrite';\nexport var modifierPhases = [beforeRead, read, afterRead, beforeMain, main, afterMain, beforeWrite, write, afterWrite];","export default function getNodeName(element) {\n return element ? (element.nodeName || '').toLowerCase() : null;\n}","export default function getWindow(node) {\n if (node == null) {\n return window;\n }\n\n if (node.toString() !== '[object Window]') {\n var ownerDocument = node.ownerDocument;\n return ownerDocument ? ownerDocument.defaultView || window : window;\n }\n\n return node;\n}","import getWindow from \"./getWindow.js\";\n\nfunction isElement(node) {\n var OwnElement = getWindow(node).Element;\n return node instanceof OwnElement || node instanceof Element;\n}\n\nfunction isHTMLElement(node) {\n var OwnElement = getWindow(node).HTMLElement;\n return node instanceof OwnElement || node instanceof HTMLElement;\n}\n\nfunction isShadowRoot(node) {\n // IE 11 has no ShadowRoot\n if (typeof ShadowRoot === 'undefined') {\n return false;\n }\n\n var OwnElement = getWindow(node).ShadowRoot;\n return node instanceof OwnElement || node instanceof ShadowRoot;\n}\n\nexport { isElement, isHTMLElement, isShadowRoot };","import getNodeName from \"../dom-utils/getNodeName.js\";\nimport { isHTMLElement } from \"../dom-utils/instanceOf.js\"; // This modifier takes the styles prepared by the `computeStyles` modifier\n// and applies them to the HTMLElements such as popper and arrow\n\nfunction applyStyles(_ref) {\n var state = _ref.state;\n Object.keys(state.elements).forEach(function (name) {\n var style = state.styles[name] || {};\n var attributes = state.attributes[name] || {};\n var element = state.elements[name]; // arrow is optional + virtual elements\n\n if (!isHTMLElement(element) || !getNodeName(element)) {\n return;\n } // Flow doesn't support to extend this property, but it's the most\n // effective way to apply styles to an HTMLElement\n // $FlowFixMe[cannot-write]\n\n\n Object.assign(element.style, style);\n Object.keys(attributes).forEach(function (name) {\n var value = attributes[name];\n\n if (value === false) {\n element.removeAttribute(name);\n } else {\n element.setAttribute(name, value === true ? '' : value);\n }\n });\n });\n}\n\nfunction effect(_ref2) {\n var state = _ref2.state;\n var initialStyles = {\n popper: {\n position: state.options.strategy,\n left: '0',\n top: '0',\n margin: '0'\n },\n arrow: {\n position: 'absolute'\n },\n reference: {}\n };\n Object.assign(state.elements.popper.style, initialStyles.popper);\n state.styles = initialStyles;\n\n if (state.elements.arrow) {\n Object.assign(state.elements.arrow.style, initialStyles.arrow);\n }\n\n return function () {\n Object.keys(state.elements).forEach(function (name) {\n var element = state.elements[name];\n var attributes = state.attributes[name] || {};\n var styleProperties = Object.keys(state.styles.hasOwnProperty(name) ? state.styles[name] : initialStyles[name]); // Set all values to an empty string to unset them\n\n var style = styleProperties.reduce(function (style, property) {\n style[property] = '';\n return style;\n }, {}); // arrow is optional + virtual elements\n\n if (!isHTMLElement(element) || !getNodeName(element)) {\n return;\n }\n\n Object.assign(element.style, style);\n Object.keys(attributes).forEach(function (attribute) {\n element.removeAttribute(attribute);\n });\n });\n };\n} // eslint-disable-next-line import/no-unused-modules\n\n\nexport default {\n name: 'applyStyles',\n enabled: true,\n phase: 'write',\n fn: applyStyles,\n effect: effect,\n requires: ['computeStyles']\n};","import { auto } from \"../enums.js\";\nexport default function getBasePlacement(placement) {\n return placement.split('-')[0];\n}","export var max = Math.max;\nexport var min = Math.min;\nexport var round = Math.round;","export default function getUAString() {\n var uaData = navigator.userAgentData;\n\n if (uaData != null && uaData.brands && Array.isArray(uaData.brands)) {\n return uaData.brands.map(function (item) {\n return item.brand + \"/\" + item.version;\n }).join(' ');\n }\n\n return navigator.userAgent;\n}","import getUAString from \"../utils/userAgent.js\";\nexport default function isLayoutViewport() {\n return !/^((?!chrome|android).)*safari/i.test(getUAString());\n}","import { isElement, isHTMLElement } from \"./instanceOf.js\";\nimport { round } from \"../utils/math.js\";\nimport getWindow from \"./getWindow.js\";\nimport isLayoutViewport from \"./isLayoutViewport.js\";\nexport default function getBoundingClientRect(element, includeScale, isFixedStrategy) {\n if (includeScale === void 0) {\n includeScale = false;\n }\n\n if (isFixedStrategy === void 0) {\n isFixedStrategy = false;\n }\n\n var clientRect = element.getBoundingClientRect();\n var scaleX = 1;\n var scaleY = 1;\n\n if (includeScale && isHTMLElement(element)) {\n scaleX = element.offsetWidth > 0 ? round(clientRect.width) / element.offsetWidth || 1 : 1;\n scaleY = element.offsetHeight > 0 ? round(clientRect.height) / element.offsetHeight || 1 : 1;\n }\n\n var _ref = isElement(element) ? getWindow(element) : window,\n visualViewport = _ref.visualViewport;\n\n var addVisualOffsets = !isLayoutViewport() && isFixedStrategy;\n var x = (clientRect.left + (addVisualOffsets && visualViewport ? visualViewport.offsetLeft : 0)) / scaleX;\n var y = (clientRect.top + (addVisualOffsets && visualViewport ? visualViewport.offsetTop : 0)) / scaleY;\n var width = clientRect.width / scaleX;\n var height = clientRect.height / scaleY;\n return {\n width: width,\n height: height,\n top: y,\n right: x + width,\n bottom: y + height,\n left: x,\n x: x,\n y: y\n };\n}","import getBoundingClientRect from \"./getBoundingClientRect.js\"; // Returns the layout rect of an element relative to its offsetParent. Layout\n// means it doesn't take into account transforms.\n\nexport default function getLayoutRect(element) {\n var clientRect = getBoundingClientRect(element); // Use the clientRect sizes if it's not been transformed.\n // Fixes https://github.com/popperjs/popper-core/issues/1223\n\n var width = element.offsetWidth;\n var height = element.offsetHeight;\n\n if (Math.abs(clientRect.width - width) <= 1) {\n width = clientRect.width;\n }\n\n if (Math.abs(clientRect.height - height) <= 1) {\n height = clientRect.height;\n }\n\n return {\n x: element.offsetLeft,\n y: element.offsetTop,\n width: width,\n height: height\n };\n}","import { isShadowRoot } from \"./instanceOf.js\";\nexport default function contains(parent, child) {\n var rootNode = child.getRootNode && child.getRootNode(); // First, attempt with faster native method\n\n if (parent.contains(child)) {\n return true;\n } // then fallback to custom implementation with Shadow DOM support\n else if (rootNode && isShadowRoot(rootNode)) {\n var next = child;\n\n do {\n if (next && parent.isSameNode(next)) {\n return true;\n } // $FlowFixMe[prop-missing]: need a better way to handle this...\n\n\n next = next.parentNode || next.host;\n } while (next);\n } // Give up, the result is false\n\n\n return false;\n}","import getWindow from \"./getWindow.js\";\nexport default function getComputedStyle(element) {\n return getWindow(element).getComputedStyle(element);\n}","import getNodeName from \"./getNodeName.js\";\nexport default function isTableElement(element) {\n return ['table', 'td', 'th'].indexOf(getNodeName(element)) >= 0;\n}","import { isElement } from \"./instanceOf.js\";\nexport default function getDocumentElement(element) {\n // $FlowFixMe[incompatible-return]: assume body is always available\n return ((isElement(element) ? element.ownerDocument : // $FlowFixMe[prop-missing]\n element.document) || window.document).documentElement;\n}","import getNodeName from \"./getNodeName.js\";\nimport getDocumentElement from \"./getDocumentElement.js\";\nimport { isShadowRoot } from \"./instanceOf.js\";\nexport default function getParentNode(element) {\n if (getNodeName(element) === 'html') {\n return element;\n }\n\n return (// this is a quicker (but less type safe) way to save quite some bytes from the bundle\n // $FlowFixMe[incompatible-return]\n // $FlowFixMe[prop-missing]\n element.assignedSlot || // step into the shadow DOM of the parent of a slotted node\n element.parentNode || ( // DOM Element detected\n isShadowRoot(element) ? element.host : null) || // ShadowRoot detected\n // $FlowFixMe[incompatible-call]: HTMLElement is a Node\n getDocumentElement(element) // fallback\n\n );\n}","import getWindow from \"./getWindow.js\";\nimport getNodeName from \"./getNodeName.js\";\nimport getComputedStyle from \"./getComputedStyle.js\";\nimport { isHTMLElement, isShadowRoot } from \"./instanceOf.js\";\nimport isTableElement from \"./isTableElement.js\";\nimport getParentNode from \"./getParentNode.js\";\nimport getUAString from \"../utils/userAgent.js\";\n\nfunction getTrueOffsetParent(element) {\n if (!isHTMLElement(element) || // https://github.com/popperjs/popper-core/issues/837\n getComputedStyle(element).position === 'fixed') {\n return null;\n }\n\n return element.offsetParent;\n} // `.offsetParent` reports `null` for fixed elements, while absolute elements\n// return the containing block\n\n\nfunction getContainingBlock(element) {\n var isFirefox = /firefox/i.test(getUAString());\n var isIE = /Trident/i.test(getUAString());\n\n if (isIE && isHTMLElement(element)) {\n // In IE 9, 10 and 11 fixed elements containing block is always established by the viewport\n var elementCss = getComputedStyle(element);\n\n if (elementCss.position === 'fixed') {\n return null;\n }\n }\n\n var currentNode = getParentNode(element);\n\n if (isShadowRoot(currentNode)) {\n currentNode = currentNode.host;\n }\n\n while (isHTMLElement(currentNode) && ['html', 'body'].indexOf(getNodeName(currentNode)) < 0) {\n var css = getComputedStyle(currentNode); // This is non-exhaustive but covers the most common CSS properties that\n // create a containing block.\n // https://developer.mozilla.org/en-US/docs/Web/CSS/Containing_block#identifying_the_containing_block\n\n if (css.transform !== 'none' || css.perspective !== 'none' || css.contain === 'paint' || ['transform', 'perspective'].indexOf(css.willChange) !== -1 || isFirefox && css.willChange === 'filter' || isFirefox && css.filter && css.filter !== 'none') {\n return currentNode;\n } else {\n currentNode = currentNode.parentNode;\n }\n }\n\n return null;\n} // Gets the closest ancestor positioned element. Handles some edge cases,\n// such as table ancestors and cross browser bugs.\n\n\nexport default function getOffsetParent(element) {\n var window = getWindow(element);\n var offsetParent = getTrueOffsetParent(element);\n\n while (offsetParent && isTableElement(offsetParent) && getComputedStyle(offsetParent).position === 'static') {\n offsetParent = getTrueOffsetParent(offsetParent);\n }\n\n if (offsetParent && (getNodeName(offsetParent) === 'html' || getNodeName(offsetParent) === 'body' && getComputedStyle(offsetParent).position === 'static')) {\n return window;\n }\n\n return offsetParent || getContainingBlock(element) || window;\n}","export default function getMainAxisFromPlacement(placement) {\n return ['top', 'bottom'].indexOf(placement) >= 0 ? 'x' : 'y';\n}","import { max as mathMax, min as mathMin } from \"./math.js\";\nexport function within(min, value, max) {\n return mathMax(min, mathMin(value, max));\n}\nexport function withinMaxClamp(min, value, max) {\n var v = within(min, value, max);\n return v > max ? max : v;\n}","import getFreshSideObject from \"./getFreshSideObject.js\";\nexport default function mergePaddingObject(paddingObject) {\n return Object.assign({}, getFreshSideObject(), paddingObject);\n}","export default function getFreshSideObject() {\n return {\n top: 0,\n right: 0,\n bottom: 0,\n left: 0\n };\n}","export default function expandToHashMap(value, keys) {\n return keys.reduce(function (hashMap, key) {\n hashMap[key] = value;\n return hashMap;\n }, {});\n}","import getBasePlacement from \"../utils/getBasePlacement.js\";\nimport getLayoutRect from \"../dom-utils/getLayoutRect.js\";\nimport contains from \"../dom-utils/contains.js\";\nimport getOffsetParent from \"../dom-utils/getOffsetParent.js\";\nimport getMainAxisFromPlacement from \"../utils/getMainAxisFromPlacement.js\";\nimport { within } from \"../utils/within.js\";\nimport mergePaddingObject from \"../utils/mergePaddingObject.js\";\nimport expandToHashMap from \"../utils/expandToHashMap.js\";\nimport { left, right, basePlacements, top, bottom } from \"../enums.js\"; // eslint-disable-next-line import/no-unused-modules\n\nvar toPaddingObject = function toPaddingObject(padding, state) {\n padding = typeof padding === 'function' ? padding(Object.assign({}, state.rects, {\n placement: state.placement\n })) : padding;\n return mergePaddingObject(typeof padding !== 'number' ? padding : expandToHashMap(padding, basePlacements));\n};\n\nfunction arrow(_ref) {\n var _state$modifiersData$;\n\n var state = _ref.state,\n name = _ref.name,\n options = _ref.options;\n var arrowElement = state.elements.arrow;\n var popperOffsets = state.modifiersData.popperOffsets;\n var basePlacement = getBasePlacement(state.placement);\n var axis = getMainAxisFromPlacement(basePlacement);\n var isVertical = [left, right].indexOf(basePlacement) >= 0;\n var len = isVertical ? 'height' : 'width';\n\n if (!arrowElement || !popperOffsets) {\n return;\n }\n\n var paddingObject = toPaddingObject(options.padding, state);\n var arrowRect = getLayoutRect(arrowElement);\n var minProp = axis === 'y' ? top : left;\n var maxProp = axis === 'y' ? bottom : right;\n var endDiff = state.rects.reference[len] + state.rects.reference[axis] - popperOffsets[axis] - state.rects.popper[len];\n var startDiff = popperOffsets[axis] - state.rects.reference[axis];\n var arrowOffsetParent = getOffsetParent(arrowElement);\n var clientSize = arrowOffsetParent ? axis === 'y' ? arrowOffsetParent.clientHeight || 0 : arrowOffsetParent.clientWidth || 0 : 0;\n var centerToReference = endDiff / 2 - startDiff / 2; // Make sure the arrow doesn't overflow the popper if the center point is\n // outside of the popper bounds\n\n var min = paddingObject[minProp];\n var max = clientSize - arrowRect[len] - paddingObject[maxProp];\n var center = clientSize / 2 - arrowRect[len] / 2 + centerToReference;\n var offset = within(min, center, max); // Prevents breaking syntax highlighting...\n\n var axisProp = axis;\n state.modifiersData[name] = (_state$modifiersData$ = {}, _state$modifiersData$[axisProp] = offset, _state$modifiersData$.centerOffset = offset - center, _state$modifiersData$);\n}\n\nfunction effect(_ref2) {\n var state = _ref2.state,\n options = _ref2.options;\n var _options$element = options.element,\n arrowElement = _options$element === void 0 ? '[data-popper-arrow]' : _options$element;\n\n if (arrowElement == null) {\n return;\n } // CSS selector\n\n\n if (typeof arrowElement === 'string') {\n arrowElement = state.elements.popper.querySelector(arrowElement);\n\n if (!arrowElement) {\n return;\n }\n }\n\n if (!contains(state.elements.popper, arrowElement)) {\n return;\n }\n\n state.elements.arrow = arrowElement;\n} // eslint-disable-next-line import/no-unused-modules\n\n\nexport default {\n name: 'arrow',\n enabled: true,\n phase: 'main',\n fn: arrow,\n effect: effect,\n requires: ['popperOffsets'],\n requiresIfExists: ['preventOverflow']\n};","export default function getVariation(placement) {\n return placement.split('-')[1];\n}","import { top, left, right, bottom, end } from \"../enums.js\";\nimport getOffsetParent from \"../dom-utils/getOffsetParent.js\";\nimport getWindow from \"../dom-utils/getWindow.js\";\nimport getDocumentElement from \"../dom-utils/getDocumentElement.js\";\nimport getComputedStyle from \"../dom-utils/getComputedStyle.js\";\nimport getBasePlacement from \"../utils/getBasePlacement.js\";\nimport getVariation from \"../utils/getVariation.js\";\nimport { round } from \"../utils/math.js\"; // eslint-disable-next-line import/no-unused-modules\n\nvar unsetSides = {\n top: 'auto',\n right: 'auto',\n bottom: 'auto',\n left: 'auto'\n}; // Round the offsets to the nearest suitable subpixel based on the DPR.\n// Zooming can change the DPR, but it seems to report a value that will\n// cleanly divide the values into the appropriate subpixels.\n\nfunction roundOffsetsByDPR(_ref, win) {\n var x = _ref.x,\n y = _ref.y;\n var dpr = win.devicePixelRatio || 1;\n return {\n x: round(x * dpr) / dpr || 0,\n y: round(y * dpr) / dpr || 0\n };\n}\n\nexport function mapToStyles(_ref2) {\n var _Object$assign2;\n\n var popper = _ref2.popper,\n popperRect = _ref2.popperRect,\n placement = _ref2.placement,\n variation = _ref2.variation,\n offsets = _ref2.offsets,\n position = _ref2.position,\n gpuAcceleration = _ref2.gpuAcceleration,\n adaptive = _ref2.adaptive,\n roundOffsets = _ref2.roundOffsets,\n isFixed = _ref2.isFixed;\n var _offsets$x = offsets.x,\n x = _offsets$x === void 0 ? 0 : _offsets$x,\n _offsets$y = offsets.y,\n y = _offsets$y === void 0 ? 0 : _offsets$y;\n\n var _ref3 = typeof roundOffsets === 'function' ? roundOffsets({\n x: x,\n y: y\n }) : {\n x: x,\n y: y\n };\n\n x = _ref3.x;\n y = _ref3.y;\n var hasX = offsets.hasOwnProperty('x');\n var hasY = offsets.hasOwnProperty('y');\n var sideX = left;\n var sideY = top;\n var win = window;\n\n if (adaptive) {\n var offsetParent = getOffsetParent(popper);\n var heightProp = 'clientHeight';\n var widthProp = 'clientWidth';\n\n if (offsetParent === getWindow(popper)) {\n offsetParent = getDocumentElement(popper);\n\n if (getComputedStyle(offsetParent).position !== 'static' && position === 'absolute') {\n heightProp = 'scrollHeight';\n widthProp = 'scrollWidth';\n }\n } // $FlowFixMe[incompatible-cast]: force type refinement, we compare offsetParent with window above, but Flow doesn't detect it\n\n\n offsetParent = offsetParent;\n\n if (placement === top || (placement === left || placement === right) && variation === end) {\n sideY = bottom;\n var offsetY = isFixed && offsetParent === win && win.visualViewport ? win.visualViewport.height : // $FlowFixMe[prop-missing]\n offsetParent[heightProp];\n y -= offsetY - popperRect.height;\n y *= gpuAcceleration ? 1 : -1;\n }\n\n if (placement === left || (placement === top || placement === bottom) && variation === end) {\n sideX = right;\n var offsetX = isFixed && offsetParent === win && win.visualViewport ? win.visualViewport.width : // $FlowFixMe[prop-missing]\n offsetParent[widthProp];\n x -= offsetX - popperRect.width;\n x *= gpuAcceleration ? 1 : -1;\n }\n }\n\n var commonStyles = Object.assign({\n position: position\n }, adaptive && unsetSides);\n\n var _ref4 = roundOffsets === true ? roundOffsetsByDPR({\n x: x,\n y: y\n }, getWindow(popper)) : {\n x: x,\n y: y\n };\n\n x = _ref4.x;\n y = _ref4.y;\n\n if (gpuAcceleration) {\n var _Object$assign;\n\n return Object.assign({}, commonStyles, (_Object$assign = {}, _Object$assign[sideY] = hasY ? '0' : '', _Object$assign[sideX] = hasX ? '0' : '', _Object$assign.transform = (win.devicePixelRatio || 1) <= 1 ? \"translate(\" + x + \"px, \" + y + \"px)\" : \"translate3d(\" + x + \"px, \" + y + \"px, 0)\", _Object$assign));\n }\n\n return Object.assign({}, commonStyles, (_Object$assign2 = {}, _Object$assign2[sideY] = hasY ? y + \"px\" : '', _Object$assign2[sideX] = hasX ? x + \"px\" : '', _Object$assign2.transform = '', _Object$assign2));\n}\n\nfunction computeStyles(_ref5) {\n var state = _ref5.state,\n options = _ref5.options;\n var _options$gpuAccelerat = options.gpuAcceleration,\n gpuAcceleration = _options$gpuAccelerat === void 0 ? true : _options$gpuAccelerat,\n _options$adaptive = options.adaptive,\n adaptive = _options$adaptive === void 0 ? true : _options$adaptive,\n _options$roundOffsets = options.roundOffsets,\n roundOffsets = _options$roundOffsets === void 0 ? true : _options$roundOffsets;\n var commonStyles = {\n placement: getBasePlacement(state.placement),\n variation: getVariation(state.placement),\n popper: state.elements.popper,\n popperRect: state.rects.popper,\n gpuAcceleration: gpuAcceleration,\n isFixed: state.options.strategy === 'fixed'\n };\n\n if (state.modifiersData.popperOffsets != null) {\n state.styles.popper = Object.assign({}, state.styles.popper, mapToStyles(Object.assign({}, commonStyles, {\n offsets: state.modifiersData.popperOffsets,\n position: state.options.strategy,\n adaptive: adaptive,\n roundOffsets: roundOffsets\n })));\n }\n\n if (state.modifiersData.arrow != null) {\n state.styles.arrow = Object.assign({}, state.styles.arrow, mapToStyles(Object.assign({}, commonStyles, {\n offsets: state.modifiersData.arrow,\n position: 'absolute',\n adaptive: false,\n roundOffsets: roundOffsets\n })));\n }\n\n state.attributes.popper = Object.assign({}, state.attributes.popper, {\n 'data-popper-placement': state.placement\n });\n} // eslint-disable-next-line import/no-unused-modules\n\n\nexport default {\n name: 'computeStyles',\n enabled: true,\n phase: 'beforeWrite',\n fn: computeStyles,\n data: {}\n};","import getWindow from \"../dom-utils/getWindow.js\"; // eslint-disable-next-line import/no-unused-modules\n\nvar passive = {\n passive: true\n};\n\nfunction effect(_ref) {\n var state = _ref.state,\n instance = _ref.instance,\n options = _ref.options;\n var _options$scroll = options.scroll,\n scroll = _options$scroll === void 0 ? true : _options$scroll,\n _options$resize = options.resize,\n resize = _options$resize === void 0 ? true : _options$resize;\n var window = getWindow(state.elements.popper);\n var scrollParents = [].concat(state.scrollParents.reference, state.scrollParents.popper);\n\n if (scroll) {\n scrollParents.forEach(function (scrollParent) {\n scrollParent.addEventListener('scroll', instance.update, passive);\n });\n }\n\n if (resize) {\n window.addEventListener('resize', instance.update, passive);\n }\n\n return function () {\n if (scroll) {\n scrollParents.forEach(function (scrollParent) {\n scrollParent.removeEventListener('scroll', instance.update, passive);\n });\n }\n\n if (resize) {\n window.removeEventListener('resize', instance.update, passive);\n }\n };\n} // eslint-disable-next-line import/no-unused-modules\n\n\nexport default {\n name: 'eventListeners',\n enabled: true,\n phase: 'write',\n fn: function fn() {},\n effect: effect,\n data: {}\n};","var hash = {\n left: 'right',\n right: 'left',\n bottom: 'top',\n top: 'bottom'\n};\nexport default function getOppositePlacement(placement) {\n return placement.replace(/left|right|bottom|top/g, function (matched) {\n return hash[matched];\n });\n}","var hash = {\n start: 'end',\n end: 'start'\n};\nexport default function getOppositeVariationPlacement(placement) {\n return placement.replace(/start|end/g, function (matched) {\n return hash[matched];\n });\n}","import getWindow from \"./getWindow.js\";\nexport default function getWindowScroll(node) {\n var win = getWindow(node);\n var scrollLeft = win.pageXOffset;\n var scrollTop = win.pageYOffset;\n return {\n scrollLeft: scrollLeft,\n scrollTop: scrollTop\n };\n}","import getBoundingClientRect from \"./getBoundingClientRect.js\";\nimport getDocumentElement from \"./getDocumentElement.js\";\nimport getWindowScroll from \"./getWindowScroll.js\";\nexport default function getWindowScrollBarX(element) {\n // If has a CSS width greater than the viewport, then this will be\n // incorrect for RTL.\n // Popper 1 is broken in this case and never had a bug report so let's assume\n // it's not an issue. I don't think anyone ever specifies width on \n // anyway.\n // Browsers where the left scrollbar doesn't cause an issue report `0` for\n // this (e.g. Edge 2019, IE11, Safari)\n return getBoundingClientRect(getDocumentElement(element)).left + getWindowScroll(element).scrollLeft;\n}","import getComputedStyle from \"./getComputedStyle.js\";\nexport default function isScrollParent(element) {\n // Firefox wants us to check `-x` and `-y` variations as well\n var _getComputedStyle = getComputedStyle(element),\n overflow = _getComputedStyle.overflow,\n overflowX = _getComputedStyle.overflowX,\n overflowY = _getComputedStyle.overflowY;\n\n return /auto|scroll|overlay|hidden/.test(overflow + overflowY + overflowX);\n}","import getParentNode from \"./getParentNode.js\";\nimport isScrollParent from \"./isScrollParent.js\";\nimport getNodeName from \"./getNodeName.js\";\nimport { isHTMLElement } from \"./instanceOf.js\";\nexport default function getScrollParent(node) {\n if (['html', 'body', '#document'].indexOf(getNodeName(node)) >= 0) {\n // $FlowFixMe[incompatible-return]: assume body is always available\n return node.ownerDocument.body;\n }\n\n if (isHTMLElement(node) && isScrollParent(node)) {\n return node;\n }\n\n return getScrollParent(getParentNode(node));\n}","import getScrollParent from \"./getScrollParent.js\";\nimport getParentNode from \"./getParentNode.js\";\nimport getWindow from \"./getWindow.js\";\nimport isScrollParent from \"./isScrollParent.js\";\n/*\ngiven a DOM element, return the list of all scroll parents, up the list of ancesors\nuntil we get to the top window object. This list is what we attach scroll listeners\nto, because if any of these parent elements scroll, we'll need to re-calculate the\nreference element's position.\n*/\n\nexport default function listScrollParents(element, list) {\n var _element$ownerDocumen;\n\n if (list === void 0) {\n list = [];\n }\n\n var scrollParent = getScrollParent(element);\n var isBody = scrollParent === ((_element$ownerDocumen = element.ownerDocument) == null ? void 0 : _element$ownerDocumen.body);\n var win = getWindow(scrollParent);\n var target = isBody ? [win].concat(win.visualViewport || [], isScrollParent(scrollParent) ? scrollParent : []) : scrollParent;\n var updatedList = list.concat(target);\n return isBody ? updatedList : // $FlowFixMe[incompatible-call]: isBody tells us target will be an HTMLElement here\n updatedList.concat(listScrollParents(getParentNode(target)));\n}","export default function rectToClientRect(rect) {\n return Object.assign({}, rect, {\n left: rect.x,\n top: rect.y,\n right: rect.x + rect.width,\n bottom: rect.y + rect.height\n });\n}","import { viewport } from \"../enums.js\";\nimport getViewportRect from \"./getViewportRect.js\";\nimport getDocumentRect from \"./getDocumentRect.js\";\nimport listScrollParents from \"./listScrollParents.js\";\nimport getOffsetParent from \"./getOffsetParent.js\";\nimport getDocumentElement from \"./getDocumentElement.js\";\nimport getComputedStyle from \"./getComputedStyle.js\";\nimport { isElement, isHTMLElement } from \"./instanceOf.js\";\nimport getBoundingClientRect from \"./getBoundingClientRect.js\";\nimport getParentNode from \"./getParentNode.js\";\nimport contains from \"./contains.js\";\nimport getNodeName from \"./getNodeName.js\";\nimport rectToClientRect from \"../utils/rectToClientRect.js\";\nimport { max, min } from \"../utils/math.js\";\n\nfunction getInnerBoundingClientRect(element, strategy) {\n var rect = getBoundingClientRect(element, false, strategy === 'fixed');\n rect.top = rect.top + element.clientTop;\n rect.left = rect.left + element.clientLeft;\n rect.bottom = rect.top + element.clientHeight;\n rect.right = rect.left + element.clientWidth;\n rect.width = element.clientWidth;\n rect.height = element.clientHeight;\n rect.x = rect.left;\n rect.y = rect.top;\n return rect;\n}\n\nfunction getClientRectFromMixedType(element, clippingParent, strategy) {\n return clippingParent === viewport ? rectToClientRect(getViewportRect(element, strategy)) : isElement(clippingParent) ? getInnerBoundingClientRect(clippingParent, strategy) : rectToClientRect(getDocumentRect(getDocumentElement(element)));\n} // A \"clipping parent\" is an overflowable container with the characteristic of\n// clipping (or hiding) overflowing elements with a position different from\n// `initial`\n\n\nfunction getClippingParents(element) {\n var clippingParents = listScrollParents(getParentNode(element));\n var canEscapeClipping = ['absolute', 'fixed'].indexOf(getComputedStyle(element).position) >= 0;\n var clipperElement = canEscapeClipping && isHTMLElement(element) ? getOffsetParent(element) : element;\n\n if (!isElement(clipperElement)) {\n return [];\n } // $FlowFixMe[incompatible-return]: https://github.com/facebook/flow/issues/1414\n\n\n return clippingParents.filter(function (clippingParent) {\n return isElement(clippingParent) && contains(clippingParent, clipperElement) && getNodeName(clippingParent) !== 'body';\n });\n} // Gets the maximum area that the element is visible in due to any number of\n// clipping parents\n\n\nexport default function getClippingRect(element, boundary, rootBoundary, strategy) {\n var mainClippingParents = boundary === 'clippingParents' ? getClippingParents(element) : [].concat(boundary);\n var clippingParents = [].concat(mainClippingParents, [rootBoundary]);\n var firstClippingParent = clippingParents[0];\n var clippingRect = clippingParents.reduce(function (accRect, clippingParent) {\n var rect = getClientRectFromMixedType(element, clippingParent, strategy);\n accRect.top = max(rect.top, accRect.top);\n accRect.right = min(rect.right, accRect.right);\n accRect.bottom = min(rect.bottom, accRect.bottom);\n accRect.left = max(rect.left, accRect.left);\n return accRect;\n }, getClientRectFromMixedType(element, firstClippingParent, strategy));\n clippingRect.width = clippingRect.right - clippingRect.left;\n clippingRect.height = clippingRect.bottom - clippingRect.top;\n clippingRect.x = clippingRect.left;\n clippingRect.y = clippingRect.top;\n return clippingRect;\n}","import getWindow from \"./getWindow.js\";\nimport getDocumentElement from \"./getDocumentElement.js\";\nimport getWindowScrollBarX from \"./getWindowScrollBarX.js\";\nimport isLayoutViewport from \"./isLayoutViewport.js\";\nexport default function getViewportRect(element, strategy) {\n var win = getWindow(element);\n var html = getDocumentElement(element);\n var visualViewport = win.visualViewport;\n var width = html.clientWidth;\n var height = html.clientHeight;\n var x = 0;\n var y = 0;\n\n if (visualViewport) {\n width = visualViewport.width;\n height = visualViewport.height;\n var layoutViewport = isLayoutViewport();\n\n if (layoutViewport || !layoutViewport && strategy === 'fixed') {\n x = visualViewport.offsetLeft;\n y = visualViewport.offsetTop;\n }\n }\n\n return {\n width: width,\n height: height,\n x: x + getWindowScrollBarX(element),\n y: y\n };\n}","import getDocumentElement from \"./getDocumentElement.js\";\nimport getComputedStyle from \"./getComputedStyle.js\";\nimport getWindowScrollBarX from \"./getWindowScrollBarX.js\";\nimport getWindowScroll from \"./getWindowScroll.js\";\nimport { max } from \"../utils/math.js\"; // Gets the entire size of the scrollable document area, even extending outside\n// of the `` and `` rect bounds if horizontally scrollable\n\nexport default function getDocumentRect(element) {\n var _element$ownerDocumen;\n\n var html = getDocumentElement(element);\n var winScroll = getWindowScroll(element);\n var body = (_element$ownerDocumen = element.ownerDocument) == null ? void 0 : _element$ownerDocumen.body;\n var width = max(html.scrollWidth, html.clientWidth, body ? body.scrollWidth : 0, body ? body.clientWidth : 0);\n var height = max(html.scrollHeight, html.clientHeight, body ? body.scrollHeight : 0, body ? body.clientHeight : 0);\n var x = -winScroll.scrollLeft + getWindowScrollBarX(element);\n var y = -winScroll.scrollTop;\n\n if (getComputedStyle(body || html).direction === 'rtl') {\n x += max(html.clientWidth, body ? body.clientWidth : 0) - width;\n }\n\n return {\n width: width,\n height: height,\n x: x,\n y: y\n };\n}","import getBasePlacement from \"./getBasePlacement.js\";\nimport getVariation from \"./getVariation.js\";\nimport getMainAxisFromPlacement from \"./getMainAxisFromPlacement.js\";\nimport { top, right, bottom, left, start, end } from \"../enums.js\";\nexport default function computeOffsets(_ref) {\n var reference = _ref.reference,\n element = _ref.element,\n placement = _ref.placement;\n var basePlacement = placement ? getBasePlacement(placement) : null;\n var variation = placement ? getVariation(placement) : null;\n var commonX = reference.x + reference.width / 2 - element.width / 2;\n var commonY = reference.y + reference.height / 2 - element.height / 2;\n var offsets;\n\n switch (basePlacement) {\n case top:\n offsets = {\n x: commonX,\n y: reference.y - element.height\n };\n break;\n\n case bottom:\n offsets = {\n x: commonX,\n y: reference.y + reference.height\n };\n break;\n\n case right:\n offsets = {\n x: reference.x + reference.width,\n y: commonY\n };\n break;\n\n case left:\n offsets = {\n x: reference.x - element.width,\n y: commonY\n };\n break;\n\n default:\n offsets = {\n x: reference.x,\n y: reference.y\n };\n }\n\n var mainAxis = basePlacement ? getMainAxisFromPlacement(basePlacement) : null;\n\n if (mainAxis != null) {\n var len = mainAxis === 'y' ? 'height' : 'width';\n\n switch (variation) {\n case start:\n offsets[mainAxis] = offsets[mainAxis] - (reference[len] / 2 - element[len] / 2);\n break;\n\n case end:\n offsets[mainAxis] = offsets[mainAxis] + (reference[len] / 2 - element[len] / 2);\n break;\n\n default:\n }\n }\n\n return offsets;\n}","import getClippingRect from \"../dom-utils/getClippingRect.js\";\nimport getDocumentElement from \"../dom-utils/getDocumentElement.js\";\nimport getBoundingClientRect from \"../dom-utils/getBoundingClientRect.js\";\nimport computeOffsets from \"./computeOffsets.js\";\nimport rectToClientRect from \"./rectToClientRect.js\";\nimport { clippingParents, reference, popper, bottom, top, right, basePlacements, viewport } from \"../enums.js\";\nimport { isElement } from \"../dom-utils/instanceOf.js\";\nimport mergePaddingObject from \"./mergePaddingObject.js\";\nimport expandToHashMap from \"./expandToHashMap.js\"; // eslint-disable-next-line import/no-unused-modules\n\nexport default function detectOverflow(state, options) {\n if (options === void 0) {\n options = {};\n }\n\n var _options = options,\n _options$placement = _options.placement,\n placement = _options$placement === void 0 ? state.placement : _options$placement,\n _options$strategy = _options.strategy,\n strategy = _options$strategy === void 0 ? state.strategy : _options$strategy,\n _options$boundary = _options.boundary,\n boundary = _options$boundary === void 0 ? clippingParents : _options$boundary,\n _options$rootBoundary = _options.rootBoundary,\n rootBoundary = _options$rootBoundary === void 0 ? viewport : _options$rootBoundary,\n _options$elementConte = _options.elementContext,\n elementContext = _options$elementConte === void 0 ? popper : _options$elementConte,\n _options$altBoundary = _options.altBoundary,\n altBoundary = _options$altBoundary === void 0 ? false : _options$altBoundary,\n _options$padding = _options.padding,\n padding = _options$padding === void 0 ? 0 : _options$padding;\n var paddingObject = mergePaddingObject(typeof padding !== 'number' ? padding : expandToHashMap(padding, basePlacements));\n var altContext = elementContext === popper ? reference : popper;\n var popperRect = state.rects.popper;\n var element = state.elements[altBoundary ? altContext : elementContext];\n var clippingClientRect = getClippingRect(isElement(element) ? element : element.contextElement || getDocumentElement(state.elements.popper), boundary, rootBoundary, strategy);\n var referenceClientRect = getBoundingClientRect(state.elements.reference);\n var popperOffsets = computeOffsets({\n reference: referenceClientRect,\n element: popperRect,\n strategy: 'absolute',\n placement: placement\n });\n var popperClientRect = rectToClientRect(Object.assign({}, popperRect, popperOffsets));\n var elementClientRect = elementContext === popper ? popperClientRect : referenceClientRect; // positive = overflowing the clipping rect\n // 0 or negative = within the clipping rect\n\n var overflowOffsets = {\n top: clippingClientRect.top - elementClientRect.top + paddingObject.top,\n bottom: elementClientRect.bottom - clippingClientRect.bottom + paddingObject.bottom,\n left: clippingClientRect.left - elementClientRect.left + paddingObject.left,\n right: elementClientRect.right - clippingClientRect.right + paddingObject.right\n };\n var offsetData = state.modifiersData.offset; // Offsets can be applied only to the popper element\n\n if (elementContext === popper && offsetData) {\n var offset = offsetData[placement];\n Object.keys(overflowOffsets).forEach(function (key) {\n var multiply = [right, bottom].indexOf(key) >= 0 ? 1 : -1;\n var axis = [top, bottom].indexOf(key) >= 0 ? 'y' : 'x';\n overflowOffsets[key] += offset[axis] * multiply;\n });\n }\n\n return overflowOffsets;\n}","import getVariation from \"./getVariation.js\";\nimport { variationPlacements, basePlacements, placements as allPlacements } from \"../enums.js\";\nimport detectOverflow from \"./detectOverflow.js\";\nimport getBasePlacement from \"./getBasePlacement.js\";\nexport default function computeAutoPlacement(state, options) {\n if (options === void 0) {\n options = {};\n }\n\n var _options = options,\n placement = _options.placement,\n boundary = _options.boundary,\n rootBoundary = _options.rootBoundary,\n padding = _options.padding,\n flipVariations = _options.flipVariations,\n _options$allowedAutoP = _options.allowedAutoPlacements,\n allowedAutoPlacements = _options$allowedAutoP === void 0 ? allPlacements : _options$allowedAutoP;\n var variation = getVariation(placement);\n var placements = variation ? flipVariations ? variationPlacements : variationPlacements.filter(function (placement) {\n return getVariation(placement) === variation;\n }) : basePlacements;\n var allowedPlacements = placements.filter(function (placement) {\n return allowedAutoPlacements.indexOf(placement) >= 0;\n });\n\n if (allowedPlacements.length === 0) {\n allowedPlacements = placements;\n } // $FlowFixMe[incompatible-type]: Flow seems to have problems with two array unions...\n\n\n var overflows = allowedPlacements.reduce(function (acc, placement) {\n acc[placement] = detectOverflow(state, {\n placement: placement,\n boundary: boundary,\n rootBoundary: rootBoundary,\n padding: padding\n })[getBasePlacement(placement)];\n return acc;\n }, {});\n return Object.keys(overflows).sort(function (a, b) {\n return overflows[a] - overflows[b];\n });\n}","import getOppositePlacement from \"../utils/getOppositePlacement.js\";\nimport getBasePlacement from \"../utils/getBasePlacement.js\";\nimport getOppositeVariationPlacement from \"../utils/getOppositeVariationPlacement.js\";\nimport detectOverflow from \"../utils/detectOverflow.js\";\nimport computeAutoPlacement from \"../utils/computeAutoPlacement.js\";\nimport { bottom, top, start, right, left, auto } from \"../enums.js\";\nimport getVariation from \"../utils/getVariation.js\"; // eslint-disable-next-line import/no-unused-modules\n\nfunction getExpandedFallbackPlacements(placement) {\n if (getBasePlacement(placement) === auto) {\n return [];\n }\n\n var oppositePlacement = getOppositePlacement(placement);\n return [getOppositeVariationPlacement(placement), oppositePlacement, getOppositeVariationPlacement(oppositePlacement)];\n}\n\nfunction flip(_ref) {\n var state = _ref.state,\n options = _ref.options,\n name = _ref.name;\n\n if (state.modifiersData[name]._skip) {\n return;\n }\n\n var _options$mainAxis = options.mainAxis,\n checkMainAxis = _options$mainAxis === void 0 ? true : _options$mainAxis,\n _options$altAxis = options.altAxis,\n checkAltAxis = _options$altAxis === void 0 ? true : _options$altAxis,\n specifiedFallbackPlacements = options.fallbackPlacements,\n padding = options.padding,\n boundary = options.boundary,\n rootBoundary = options.rootBoundary,\n altBoundary = options.altBoundary,\n _options$flipVariatio = options.flipVariations,\n flipVariations = _options$flipVariatio === void 0 ? true : _options$flipVariatio,\n allowedAutoPlacements = options.allowedAutoPlacements;\n var preferredPlacement = state.options.placement;\n var basePlacement = getBasePlacement(preferredPlacement);\n var isBasePlacement = basePlacement === preferredPlacement;\n var fallbackPlacements = specifiedFallbackPlacements || (isBasePlacement || !flipVariations ? [getOppositePlacement(preferredPlacement)] : getExpandedFallbackPlacements(preferredPlacement));\n var placements = [preferredPlacement].concat(fallbackPlacements).reduce(function (acc, placement) {\n return acc.concat(getBasePlacement(placement) === auto ? computeAutoPlacement(state, {\n placement: placement,\n boundary: boundary,\n rootBoundary: rootBoundary,\n padding: padding,\n flipVariations: flipVariations,\n allowedAutoPlacements: allowedAutoPlacements\n }) : placement);\n }, []);\n var referenceRect = state.rects.reference;\n var popperRect = state.rects.popper;\n var checksMap = new Map();\n var makeFallbackChecks = true;\n var firstFittingPlacement = placements[0];\n\n for (var i = 0; i < placements.length; i++) {\n var placement = placements[i];\n\n var _basePlacement = getBasePlacement(placement);\n\n var isStartVariation = getVariation(placement) === start;\n var isVertical = [top, bottom].indexOf(_basePlacement) >= 0;\n var len = isVertical ? 'width' : 'height';\n var overflow = detectOverflow(state, {\n placement: placement,\n boundary: boundary,\n rootBoundary: rootBoundary,\n altBoundary: altBoundary,\n padding: padding\n });\n var mainVariationSide = isVertical ? isStartVariation ? right : left : isStartVariation ? bottom : top;\n\n if (referenceRect[len] > popperRect[len]) {\n mainVariationSide = getOppositePlacement(mainVariationSide);\n }\n\n var altVariationSide = getOppositePlacement(mainVariationSide);\n var checks = [];\n\n if (checkMainAxis) {\n checks.push(overflow[_basePlacement] <= 0);\n }\n\n if (checkAltAxis) {\n checks.push(overflow[mainVariationSide] <= 0, overflow[altVariationSide] <= 0);\n }\n\n if (checks.every(function (check) {\n return check;\n })) {\n firstFittingPlacement = placement;\n makeFallbackChecks = false;\n break;\n }\n\n checksMap.set(placement, checks);\n }\n\n if (makeFallbackChecks) {\n // `2` may be desired in some cases – research later\n var numberOfChecks = flipVariations ? 3 : 1;\n\n var _loop = function _loop(_i) {\n var fittingPlacement = placements.find(function (placement) {\n var checks = checksMap.get(placement);\n\n if (checks) {\n return checks.slice(0, _i).every(function (check) {\n return check;\n });\n }\n });\n\n if (fittingPlacement) {\n firstFittingPlacement = fittingPlacement;\n return \"break\";\n }\n };\n\n for (var _i = numberOfChecks; _i > 0; _i--) {\n var _ret = _loop(_i);\n\n if (_ret === \"break\") break;\n }\n }\n\n if (state.placement !== firstFittingPlacement) {\n state.modifiersData[name]._skip = true;\n state.placement = firstFittingPlacement;\n state.reset = true;\n }\n} // eslint-disable-next-line import/no-unused-modules\n\n\nexport default {\n name: 'flip',\n enabled: true,\n phase: 'main',\n fn: flip,\n requiresIfExists: ['offset'],\n data: {\n _skip: false\n }\n};","import { top, bottom, left, right } from \"../enums.js\";\nimport detectOverflow from \"../utils/detectOverflow.js\";\n\nfunction getSideOffsets(overflow, rect, preventedOffsets) {\n if (preventedOffsets === void 0) {\n preventedOffsets = {\n x: 0,\n y: 0\n };\n }\n\n return {\n top: overflow.top - rect.height - preventedOffsets.y,\n right: overflow.right - rect.width + preventedOffsets.x,\n bottom: overflow.bottom - rect.height + preventedOffsets.y,\n left: overflow.left - rect.width - preventedOffsets.x\n };\n}\n\nfunction isAnySideFullyClipped(overflow) {\n return [top, right, bottom, left].some(function (side) {\n return overflow[side] >= 0;\n });\n}\n\nfunction hide(_ref) {\n var state = _ref.state,\n name = _ref.name;\n var referenceRect = state.rects.reference;\n var popperRect = state.rects.popper;\n var preventedOffsets = state.modifiersData.preventOverflow;\n var referenceOverflow = detectOverflow(state, {\n elementContext: 'reference'\n });\n var popperAltOverflow = detectOverflow(state, {\n altBoundary: true\n });\n var referenceClippingOffsets = getSideOffsets(referenceOverflow, referenceRect);\n var popperEscapeOffsets = getSideOffsets(popperAltOverflow, popperRect, preventedOffsets);\n var isReferenceHidden = isAnySideFullyClipped(referenceClippingOffsets);\n var hasPopperEscaped = isAnySideFullyClipped(popperEscapeOffsets);\n state.modifiersData[name] = {\n referenceClippingOffsets: referenceClippingOffsets,\n popperEscapeOffsets: popperEscapeOffsets,\n isReferenceHidden: isReferenceHidden,\n hasPopperEscaped: hasPopperEscaped\n };\n state.attributes.popper = Object.assign({}, state.attributes.popper, {\n 'data-popper-reference-hidden': isReferenceHidden,\n 'data-popper-escaped': hasPopperEscaped\n });\n} // eslint-disable-next-line import/no-unused-modules\n\n\nexport default {\n name: 'hide',\n enabled: true,\n phase: 'main',\n requiresIfExists: ['preventOverflow'],\n fn: hide\n};","import getBasePlacement from \"../utils/getBasePlacement.js\";\nimport { top, left, right, placements } from \"../enums.js\"; // eslint-disable-next-line import/no-unused-modules\n\nexport function distanceAndSkiddingToXY(placement, rects, offset) {\n var basePlacement = getBasePlacement(placement);\n var invertDistance = [left, top].indexOf(basePlacement) >= 0 ? -1 : 1;\n\n var _ref = typeof offset === 'function' ? offset(Object.assign({}, rects, {\n placement: placement\n })) : offset,\n skidding = _ref[0],\n distance = _ref[1];\n\n skidding = skidding || 0;\n distance = (distance || 0) * invertDistance;\n return [left, right].indexOf(basePlacement) >= 0 ? {\n x: distance,\n y: skidding\n } : {\n x: skidding,\n y: distance\n };\n}\n\nfunction offset(_ref2) {\n var state = _ref2.state,\n options = _ref2.options,\n name = _ref2.name;\n var _options$offset = options.offset,\n offset = _options$offset === void 0 ? [0, 0] : _options$offset;\n var data = placements.reduce(function (acc, placement) {\n acc[placement] = distanceAndSkiddingToXY(placement, state.rects, offset);\n return acc;\n }, {});\n var _data$state$placement = data[state.placement],\n x = _data$state$placement.x,\n y = _data$state$placement.y;\n\n if (state.modifiersData.popperOffsets != null) {\n state.modifiersData.popperOffsets.x += x;\n state.modifiersData.popperOffsets.y += y;\n }\n\n state.modifiersData[name] = data;\n} // eslint-disable-next-line import/no-unused-modules\n\n\nexport default {\n name: 'offset',\n enabled: true,\n phase: 'main',\n requires: ['popperOffsets'],\n fn: offset\n};","import computeOffsets from \"../utils/computeOffsets.js\";\n\nfunction popperOffsets(_ref) {\n var state = _ref.state,\n name = _ref.name;\n // Offsets are the actual position the popper needs to have to be\n // properly positioned near its reference element\n // This is the most basic placement, and will be adjusted by\n // the modifiers in the next step\n state.modifiersData[name] = computeOffsets({\n reference: state.rects.reference,\n element: state.rects.popper,\n strategy: 'absolute',\n placement: state.placement\n });\n} // eslint-disable-next-line import/no-unused-modules\n\n\nexport default {\n name: 'popperOffsets',\n enabled: true,\n phase: 'read',\n fn: popperOffsets,\n data: {}\n};","import { top, left, right, bottom, start } from \"../enums.js\";\nimport getBasePlacement from \"../utils/getBasePlacement.js\";\nimport getMainAxisFromPlacement from \"../utils/getMainAxisFromPlacement.js\";\nimport getAltAxis from \"../utils/getAltAxis.js\";\nimport { within, withinMaxClamp } from \"../utils/within.js\";\nimport getLayoutRect from \"../dom-utils/getLayoutRect.js\";\nimport getOffsetParent from \"../dom-utils/getOffsetParent.js\";\nimport detectOverflow from \"../utils/detectOverflow.js\";\nimport getVariation from \"../utils/getVariation.js\";\nimport getFreshSideObject from \"../utils/getFreshSideObject.js\";\nimport { min as mathMin, max as mathMax } from \"../utils/math.js\";\n\nfunction preventOverflow(_ref) {\n var state = _ref.state,\n options = _ref.options,\n name = _ref.name;\n var _options$mainAxis = options.mainAxis,\n checkMainAxis = _options$mainAxis === void 0 ? true : _options$mainAxis,\n _options$altAxis = options.altAxis,\n checkAltAxis = _options$altAxis === void 0 ? false : _options$altAxis,\n boundary = options.boundary,\n rootBoundary = options.rootBoundary,\n altBoundary = options.altBoundary,\n padding = options.padding,\n _options$tether = options.tether,\n tether = _options$tether === void 0 ? true : _options$tether,\n _options$tetherOffset = options.tetherOffset,\n tetherOffset = _options$tetherOffset === void 0 ? 0 : _options$tetherOffset;\n var overflow = detectOverflow(state, {\n boundary: boundary,\n rootBoundary: rootBoundary,\n padding: padding,\n altBoundary: altBoundary\n });\n var basePlacement = getBasePlacement(state.placement);\n var variation = getVariation(state.placement);\n var isBasePlacement = !variation;\n var mainAxis = getMainAxisFromPlacement(basePlacement);\n var altAxis = getAltAxis(mainAxis);\n var popperOffsets = state.modifiersData.popperOffsets;\n var referenceRect = state.rects.reference;\n var popperRect = state.rects.popper;\n var tetherOffsetValue = typeof tetherOffset === 'function' ? tetherOffset(Object.assign({}, state.rects, {\n placement: state.placement\n })) : tetherOffset;\n var normalizedTetherOffsetValue = typeof tetherOffsetValue === 'number' ? {\n mainAxis: tetherOffsetValue,\n altAxis: tetherOffsetValue\n } : Object.assign({\n mainAxis: 0,\n altAxis: 0\n }, tetherOffsetValue);\n var offsetModifierState = state.modifiersData.offset ? state.modifiersData.offset[state.placement] : null;\n var data = {\n x: 0,\n y: 0\n };\n\n if (!popperOffsets) {\n return;\n }\n\n if (checkMainAxis) {\n var _offsetModifierState$;\n\n var mainSide = mainAxis === 'y' ? top : left;\n var altSide = mainAxis === 'y' ? bottom : right;\n var len = mainAxis === 'y' ? 'height' : 'width';\n var offset = popperOffsets[mainAxis];\n var min = offset + overflow[mainSide];\n var max = offset - overflow[altSide];\n var additive = tether ? -popperRect[len] / 2 : 0;\n var minLen = variation === start ? referenceRect[len] : popperRect[len];\n var maxLen = variation === start ? -popperRect[len] : -referenceRect[len]; // We need to include the arrow in the calculation so the arrow doesn't go\n // outside the reference bounds\n\n var arrowElement = state.elements.arrow;\n var arrowRect = tether && arrowElement ? getLayoutRect(arrowElement) : {\n width: 0,\n height: 0\n };\n var arrowPaddingObject = state.modifiersData['arrow#persistent'] ? state.modifiersData['arrow#persistent'].padding : getFreshSideObject();\n var arrowPaddingMin = arrowPaddingObject[mainSide];\n var arrowPaddingMax = arrowPaddingObject[altSide]; // If the reference length is smaller than the arrow length, we don't want\n // to include its full size in the calculation. If the reference is small\n // and near the edge of a boundary, the popper can overflow even if the\n // reference is not overflowing as well (e.g. virtual elements with no\n // width or height)\n\n var arrowLen = within(0, referenceRect[len], arrowRect[len]);\n var minOffset = isBasePlacement ? referenceRect[len] / 2 - additive - arrowLen - arrowPaddingMin - normalizedTetherOffsetValue.mainAxis : minLen - arrowLen - arrowPaddingMin - normalizedTetherOffsetValue.mainAxis;\n var maxOffset = isBasePlacement ? -referenceRect[len] / 2 + additive + arrowLen + arrowPaddingMax + normalizedTetherOffsetValue.mainAxis : maxLen + arrowLen + arrowPaddingMax + normalizedTetherOffsetValue.mainAxis;\n var arrowOffsetParent = state.elements.arrow && getOffsetParent(state.elements.arrow);\n var clientOffset = arrowOffsetParent ? mainAxis === 'y' ? arrowOffsetParent.clientTop || 0 : arrowOffsetParent.clientLeft || 0 : 0;\n var offsetModifierValue = (_offsetModifierState$ = offsetModifierState == null ? void 0 : offsetModifierState[mainAxis]) != null ? _offsetModifierState$ : 0;\n var tetherMin = offset + minOffset - offsetModifierValue - clientOffset;\n var tetherMax = offset + maxOffset - offsetModifierValue;\n var preventedOffset = within(tether ? mathMin(min, tetherMin) : min, offset, tether ? mathMax(max, tetherMax) : max);\n popperOffsets[mainAxis] = preventedOffset;\n data[mainAxis] = preventedOffset - offset;\n }\n\n if (checkAltAxis) {\n var _offsetModifierState$2;\n\n var _mainSide = mainAxis === 'x' ? top : left;\n\n var _altSide = mainAxis === 'x' ? bottom : right;\n\n var _offset = popperOffsets[altAxis];\n\n var _len = altAxis === 'y' ? 'height' : 'width';\n\n var _min = _offset + overflow[_mainSide];\n\n var _max = _offset - overflow[_altSide];\n\n var isOriginSide = [top, left].indexOf(basePlacement) !== -1;\n\n var _offsetModifierValue = (_offsetModifierState$2 = offsetModifierState == null ? void 0 : offsetModifierState[altAxis]) != null ? _offsetModifierState$2 : 0;\n\n var _tetherMin = isOriginSide ? _min : _offset - referenceRect[_len] - popperRect[_len] - _offsetModifierValue + normalizedTetherOffsetValue.altAxis;\n\n var _tetherMax = isOriginSide ? _offset + referenceRect[_len] + popperRect[_len] - _offsetModifierValue - normalizedTetherOffsetValue.altAxis : _max;\n\n var _preventedOffset = tether && isOriginSide ? withinMaxClamp(_tetherMin, _offset, _tetherMax) : within(tether ? _tetherMin : _min, _offset, tether ? _tetherMax : _max);\n\n popperOffsets[altAxis] = _preventedOffset;\n data[altAxis] = _preventedOffset - _offset;\n }\n\n state.modifiersData[name] = data;\n} // eslint-disable-next-line import/no-unused-modules\n\n\nexport default {\n name: 'preventOverflow',\n enabled: true,\n phase: 'main',\n fn: preventOverflow,\n requiresIfExists: ['offset']\n};","export default function getAltAxis(axis) {\n return axis === 'x' ? 'y' : 'x';\n}","import getBoundingClientRect from \"./getBoundingClientRect.js\";\nimport getNodeScroll from \"./getNodeScroll.js\";\nimport getNodeName from \"./getNodeName.js\";\nimport { isHTMLElement } from \"./instanceOf.js\";\nimport getWindowScrollBarX from \"./getWindowScrollBarX.js\";\nimport getDocumentElement from \"./getDocumentElement.js\";\nimport isScrollParent from \"./isScrollParent.js\";\nimport { round } from \"../utils/math.js\";\n\nfunction isElementScaled(element) {\n var rect = element.getBoundingClientRect();\n var scaleX = round(rect.width) / element.offsetWidth || 1;\n var scaleY = round(rect.height) / element.offsetHeight || 1;\n return scaleX !== 1 || scaleY !== 1;\n} // Returns the composite rect of an element relative to its offsetParent.\n// Composite means it takes into account transforms as well as layout.\n\n\nexport default function getCompositeRect(elementOrVirtualElement, offsetParent, isFixed) {\n if (isFixed === void 0) {\n isFixed = false;\n }\n\n var isOffsetParentAnElement = isHTMLElement(offsetParent);\n var offsetParentIsScaled = isHTMLElement(offsetParent) && isElementScaled(offsetParent);\n var documentElement = getDocumentElement(offsetParent);\n var rect = getBoundingClientRect(elementOrVirtualElement, offsetParentIsScaled, isFixed);\n var scroll = {\n scrollLeft: 0,\n scrollTop: 0\n };\n var offsets = {\n x: 0,\n y: 0\n };\n\n if (isOffsetParentAnElement || !isOffsetParentAnElement && !isFixed) {\n if (getNodeName(offsetParent) !== 'body' || // https://github.com/popperjs/popper-core/issues/1078\n isScrollParent(documentElement)) {\n scroll = getNodeScroll(offsetParent);\n }\n\n if (isHTMLElement(offsetParent)) {\n offsets = getBoundingClientRect(offsetParent, true);\n offsets.x += offsetParent.clientLeft;\n offsets.y += offsetParent.clientTop;\n } else if (documentElement) {\n offsets.x = getWindowScrollBarX(documentElement);\n }\n }\n\n return {\n x: rect.left + scroll.scrollLeft - offsets.x,\n y: rect.top + scroll.scrollTop - offsets.y,\n width: rect.width,\n height: rect.height\n };\n}","import getWindowScroll from \"./getWindowScroll.js\";\nimport getWindow from \"./getWindow.js\";\nimport { isHTMLElement } from \"./instanceOf.js\";\nimport getHTMLElementScroll from \"./getHTMLElementScroll.js\";\nexport default function getNodeScroll(node) {\n if (node === getWindow(node) || !isHTMLElement(node)) {\n return getWindowScroll(node);\n } else {\n return getHTMLElementScroll(node);\n }\n}","export default function getHTMLElementScroll(element) {\n return {\n scrollLeft: element.scrollLeft,\n scrollTop: element.scrollTop\n };\n}","import { modifierPhases } from \"../enums.js\"; // source: https://stackoverflow.com/questions/49875255\n\nfunction order(modifiers) {\n var map = new Map();\n var visited = new Set();\n var result = [];\n modifiers.forEach(function (modifier) {\n map.set(modifier.name, modifier);\n }); // On visiting object, check for its dependencies and visit them recursively\n\n function sort(modifier) {\n visited.add(modifier.name);\n var requires = [].concat(modifier.requires || [], modifier.requiresIfExists || []);\n requires.forEach(function (dep) {\n if (!visited.has(dep)) {\n var depModifier = map.get(dep);\n\n if (depModifier) {\n sort(depModifier);\n }\n }\n });\n result.push(modifier);\n }\n\n modifiers.forEach(function (modifier) {\n if (!visited.has(modifier.name)) {\n // check for visited object\n sort(modifier);\n }\n });\n return result;\n}\n\nexport default function orderModifiers(modifiers) {\n // order based on dependencies\n var orderedModifiers = order(modifiers); // order based on phase\n\n return modifierPhases.reduce(function (acc, phase) {\n return acc.concat(orderedModifiers.filter(function (modifier) {\n return modifier.phase === phase;\n }));\n }, []);\n}","import getCompositeRect from \"./dom-utils/getCompositeRect.js\";\nimport getLayoutRect from \"./dom-utils/getLayoutRect.js\";\nimport listScrollParents from \"./dom-utils/listScrollParents.js\";\nimport getOffsetParent from \"./dom-utils/getOffsetParent.js\";\nimport orderModifiers from \"./utils/orderModifiers.js\";\nimport debounce from \"./utils/debounce.js\";\nimport mergeByName from \"./utils/mergeByName.js\";\nimport detectOverflow from \"./utils/detectOverflow.js\";\nimport { isElement } from \"./dom-utils/instanceOf.js\";\nvar DEFAULT_OPTIONS = {\n placement: 'bottom',\n modifiers: [],\n strategy: 'absolute'\n};\n\nfunction areValidElements() {\n for (var _len = arguments.length, args = new Array(_len), _key = 0; _key < _len; _key++) {\n args[_key] = arguments[_key];\n }\n\n return !args.some(function (element) {\n return !(element && typeof element.getBoundingClientRect === 'function');\n });\n}\n\nexport function popperGenerator(generatorOptions) {\n if (generatorOptions === void 0) {\n generatorOptions = {};\n }\n\n var _generatorOptions = generatorOptions,\n _generatorOptions$def = _generatorOptions.defaultModifiers,\n defaultModifiers = _generatorOptions$def === void 0 ? [] : _generatorOptions$def,\n _generatorOptions$def2 = _generatorOptions.defaultOptions,\n defaultOptions = _generatorOptions$def2 === void 0 ? DEFAULT_OPTIONS : _generatorOptions$def2;\n return function createPopper(reference, popper, options) {\n if (options === void 0) {\n options = defaultOptions;\n }\n\n var state = {\n placement: 'bottom',\n orderedModifiers: [],\n options: Object.assign({}, DEFAULT_OPTIONS, defaultOptions),\n modifiersData: {},\n elements: {\n reference: reference,\n popper: popper\n },\n attributes: {},\n styles: {}\n };\n var effectCleanupFns = [];\n var isDestroyed = false;\n var instance = {\n state: state,\n setOptions: function setOptions(setOptionsAction) {\n var options = typeof setOptionsAction === 'function' ? setOptionsAction(state.options) : setOptionsAction;\n cleanupModifierEffects();\n state.options = Object.assign({}, defaultOptions, state.options, options);\n state.scrollParents = {\n reference: isElement(reference) ? listScrollParents(reference) : reference.contextElement ? listScrollParents(reference.contextElement) : [],\n popper: listScrollParents(popper)\n }; // Orders the modifiers based on their dependencies and `phase`\n // properties\n\n var orderedModifiers = orderModifiers(mergeByName([].concat(defaultModifiers, state.options.modifiers))); // Strip out disabled modifiers\n\n state.orderedModifiers = orderedModifiers.filter(function (m) {\n return m.enabled;\n });\n runModifierEffects();\n return instance.update();\n },\n // Sync update – it will always be executed, even if not necessary. This\n // is useful for low frequency updates where sync behavior simplifies the\n // logic.\n // For high frequency updates (e.g. `resize` and `scroll` events), always\n // prefer the async Popper#update method\n forceUpdate: function forceUpdate() {\n if (isDestroyed) {\n return;\n }\n\n var _state$elements = state.elements,\n reference = _state$elements.reference,\n popper = _state$elements.popper; // Don't proceed if `reference` or `popper` are not valid elements\n // anymore\n\n if (!areValidElements(reference, popper)) {\n return;\n } // Store the reference and popper rects to be read by modifiers\n\n\n state.rects = {\n reference: getCompositeRect(reference, getOffsetParent(popper), state.options.strategy === 'fixed'),\n popper: getLayoutRect(popper)\n }; // Modifiers have the ability to reset the current update cycle. The\n // most common use case for this is the `flip` modifier changing the\n // placement, which then needs to re-run all the modifiers, because the\n // logic was previously ran for the previous placement and is therefore\n // stale/incorrect\n\n state.reset = false;\n state.placement = state.options.placement; // On each update cycle, the `modifiersData` property for each modifier\n // is filled with the initial data specified by the modifier. This means\n // it doesn't persist and is fresh on each update.\n // To ensure persistent data, use `${name}#persistent`\n\n state.orderedModifiers.forEach(function (modifier) {\n return state.modifiersData[modifier.name] = Object.assign({}, modifier.data);\n });\n\n for (var index = 0; index < state.orderedModifiers.length; index++) {\n if (state.reset === true) {\n state.reset = false;\n index = -1;\n continue;\n }\n\n var _state$orderedModifie = state.orderedModifiers[index],\n fn = _state$orderedModifie.fn,\n _state$orderedModifie2 = _state$orderedModifie.options,\n _options = _state$orderedModifie2 === void 0 ? {} : _state$orderedModifie2,\n name = _state$orderedModifie.name;\n\n if (typeof fn === 'function') {\n state = fn({\n state: state,\n options: _options,\n name: name,\n instance: instance\n }) || state;\n }\n }\n },\n // Async and optimistically optimized update – it will not be executed if\n // not necessary (debounced to run at most once-per-tick)\n update: debounce(function () {\n return new Promise(function (resolve) {\n instance.forceUpdate();\n resolve(state);\n });\n }),\n destroy: function destroy() {\n cleanupModifierEffects();\n isDestroyed = true;\n }\n };\n\n if (!areValidElements(reference, popper)) {\n return instance;\n }\n\n instance.setOptions(options).then(function (state) {\n if (!isDestroyed && options.onFirstUpdate) {\n options.onFirstUpdate(state);\n }\n }); // Modifiers have the ability to execute arbitrary code before the first\n // update cycle runs. They will be executed in the same order as the update\n // cycle. This is useful when a modifier adds some persistent data that\n // other modifiers need to use, but the modifier is run after the dependent\n // one.\n\n function runModifierEffects() {\n state.orderedModifiers.forEach(function (_ref) {\n var name = _ref.name,\n _ref$options = _ref.options,\n options = _ref$options === void 0 ? {} : _ref$options,\n effect = _ref.effect;\n\n if (typeof effect === 'function') {\n var cleanupFn = effect({\n state: state,\n name: name,\n instance: instance,\n options: options\n });\n\n var noopFn = function noopFn() {};\n\n effectCleanupFns.push(cleanupFn || noopFn);\n }\n });\n }\n\n function cleanupModifierEffects() {\n effectCleanupFns.forEach(function (fn) {\n return fn();\n });\n effectCleanupFns = [];\n }\n\n return instance;\n };\n}\nexport var createPopper = /*#__PURE__*/popperGenerator(); // eslint-disable-next-line import/no-unused-modules\n\nexport { detectOverflow };","export default function debounce(fn) {\n var pending;\n return function () {\n if (!pending) {\n pending = new Promise(function (resolve) {\n Promise.resolve().then(function () {\n pending = undefined;\n resolve(fn());\n });\n });\n }\n\n return pending;\n };\n}","export default function mergeByName(modifiers) {\n var merged = modifiers.reduce(function (merged, current) {\n var existing = merged[current.name];\n merged[current.name] = existing ? Object.assign({}, existing, current, {\n options: Object.assign({}, existing.options, current.options),\n data: Object.assign({}, existing.data, current.data)\n }) : current;\n return merged;\n }, {}); // IE11 does not support Object.values\n\n return Object.keys(merged).map(function (key) {\n return merged[key];\n });\n}","import { popperGenerator, detectOverflow } from \"./createPopper.js\";\nimport eventListeners from \"./modifiers/eventListeners.js\";\nimport popperOffsets from \"./modifiers/popperOffsets.js\";\nimport computeStyles from \"./modifiers/computeStyles.js\";\nimport applyStyles from \"./modifiers/applyStyles.js\";\nvar defaultModifiers = [eventListeners, popperOffsets, computeStyles, applyStyles];\nvar createPopper = /*#__PURE__*/popperGenerator({\n defaultModifiers: defaultModifiers\n}); // eslint-disable-next-line import/no-unused-modules\n\nexport { createPopper, popperGenerator, defaultModifiers, detectOverflow };","import { popperGenerator, detectOverflow } from \"./createPopper.js\";\nimport eventListeners from \"./modifiers/eventListeners.js\";\nimport popperOffsets from \"./modifiers/popperOffsets.js\";\nimport computeStyles from \"./modifiers/computeStyles.js\";\nimport applyStyles from \"./modifiers/applyStyles.js\";\nimport offset from \"./modifiers/offset.js\";\nimport flip from \"./modifiers/flip.js\";\nimport preventOverflow from \"./modifiers/preventOverflow.js\";\nimport arrow from \"./modifiers/arrow.js\";\nimport hide from \"./modifiers/hide.js\";\nvar defaultModifiers = [eventListeners, popperOffsets, computeStyles, applyStyles, offset, flip, preventOverflow, arrow, hide];\nvar createPopper = /*#__PURE__*/popperGenerator({\n defaultModifiers: defaultModifiers\n}); // eslint-disable-next-line import/no-unused-modules\n\nexport { createPopper, popperGenerator, defaultModifiers, detectOverflow }; // eslint-disable-next-line import/no-unused-modules\n\nexport { createPopper as createPopperLite } from \"./popper-lite.js\"; // eslint-disable-next-line import/no-unused-modules\n\nexport * from \"./modifiers/index.js\";","/**\n * --------------------------------------------------------------------------\n * Bootstrap dropdown.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport * as Popper from '@popperjs/core'\nimport BaseComponent from './base-component.js'\nimport EventHandler from './dom/event-handler.js'\nimport Manipulator from './dom/manipulator.js'\nimport SelectorEngine from './dom/selector-engine.js'\nimport {\n defineJQueryPlugin,\n execute,\n getElement,\n getNextActiveElement,\n isDisabled,\n isElement,\n isRTL,\n isVisible,\n noop\n} from './util/index.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'dropdown'\nconst DATA_KEY = 'bs.dropdown'\nconst EVENT_KEY = `.${DATA_KEY}`\nconst DATA_API_KEY = '.data-api'\n\nconst ESCAPE_KEY = 'Escape'\nconst TAB_KEY = 'Tab'\nconst ARROW_UP_KEY = 'ArrowUp'\nconst ARROW_DOWN_KEY = 'ArrowDown'\nconst RIGHT_MOUSE_BUTTON = 2 // MouseEvent.button value for the secondary button, usually the right button\n\nconst EVENT_HIDE = `hide${EVENT_KEY}`\nconst EVENT_HIDDEN = `hidden${EVENT_KEY}`\nconst EVENT_SHOW = `show${EVENT_KEY}`\nconst EVENT_SHOWN = `shown${EVENT_KEY}`\nconst EVENT_CLICK_DATA_API = `click${EVENT_KEY}${DATA_API_KEY}`\nconst EVENT_KEYDOWN_DATA_API = `keydown${EVENT_KEY}${DATA_API_KEY}`\nconst EVENT_KEYUP_DATA_API = `keyup${EVENT_KEY}${DATA_API_KEY}`\n\nconst CLASS_NAME_SHOW = 'show'\nconst CLASS_NAME_DROPUP = 'dropup'\nconst CLASS_NAME_DROPEND = 'dropend'\nconst CLASS_NAME_DROPSTART = 'dropstart'\nconst CLASS_NAME_DROPUP_CENTER = 'dropup-center'\nconst CLASS_NAME_DROPDOWN_CENTER = 'dropdown-center'\n\nconst SELECTOR_DATA_TOGGLE = '[data-bs-toggle=\"dropdown\"]:not(.disabled):not(:disabled)'\nconst SELECTOR_DATA_TOGGLE_SHOWN = `${SELECTOR_DATA_TOGGLE}.${CLASS_NAME_SHOW}`\nconst SELECTOR_MENU = '.dropdown-menu'\nconst SELECTOR_NAVBAR = '.navbar'\nconst SELECTOR_NAVBAR_NAV = '.navbar-nav'\nconst SELECTOR_VISIBLE_ITEMS = '.dropdown-menu .dropdown-item:not(.disabled):not(:disabled)'\n\nconst PLACEMENT_TOP = isRTL() ? 'top-end' : 'top-start'\nconst PLACEMENT_TOPEND = isRTL() ? 'top-start' : 'top-end'\nconst PLACEMENT_BOTTOM = isRTL() ? 'bottom-end' : 'bottom-start'\nconst PLACEMENT_BOTTOMEND = isRTL() ? 'bottom-start' : 'bottom-end'\nconst PLACEMENT_RIGHT = isRTL() ? 'left-start' : 'right-start'\nconst PLACEMENT_LEFT = isRTL() ? 'right-start' : 'left-start'\nconst PLACEMENT_TOPCENTER = 'top'\nconst PLACEMENT_BOTTOMCENTER = 'bottom'\n\nconst Default = {\n autoClose: true,\n boundary: 'clippingParents',\n display: 'dynamic',\n offset: [0, 2],\n popperConfig: null,\n reference: 'toggle'\n}\n\nconst DefaultType = {\n autoClose: '(boolean|string)',\n boundary: '(string|element)',\n display: 'string',\n offset: '(array|string|function)',\n popperConfig: '(null|object|function)',\n reference: '(string|element|object)'\n}\n\n/**\n * Class definition\n */\n\nclass Dropdown extends BaseComponent {\n constructor(element, config) {\n super(element, config)\n\n this._popper = null\n this._parent = this._element.parentNode // dropdown wrapper\n // TODO: v6 revert #37011 & change markup https://getbootstrap.com/docs/5.3/forms/input-group/\n this._menu = SelectorEngine.next(this._element, SELECTOR_MENU)[0] ||\n SelectorEngine.prev(this._element, SELECTOR_MENU)[0] ||\n SelectorEngine.findOne(SELECTOR_MENU, this._parent)\n this._inNavbar = this._detectNavbar()\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n toggle() {\n return this._isShown() ? this.hide() : this.show()\n }\n\n show() {\n if (isDisabled(this._element) || this._isShown()) {\n return\n }\n\n const relatedTarget = {\n relatedTarget: this._element\n }\n\n const showEvent = EventHandler.trigger(this._element, EVENT_SHOW, relatedTarget)\n\n if (showEvent.defaultPrevented) {\n return\n }\n\n this._createPopper()\n\n // If this is a touch-enabled device we add extra\n // empty mouseover listeners to the body's immediate children;\n // only needed because of broken event delegation on iOS\n // https://www.quirksmode.org/blog/archives/2014/02/mouse_event_bub.html\n if ('ontouchstart' in document.documentElement && !this._parent.closest(SELECTOR_NAVBAR_NAV)) {\n for (const element of [].concat(...document.body.children)) {\n EventHandler.on(element, 'mouseover', noop)\n }\n }\n\n this._element.focus()\n this._element.setAttribute('aria-expanded', true)\n\n this._menu.classList.add(CLASS_NAME_SHOW)\n this._element.classList.add(CLASS_NAME_SHOW)\n EventHandler.trigger(this._element, EVENT_SHOWN, relatedTarget)\n }\n\n hide() {\n if (isDisabled(this._element) || !this._isShown()) {\n return\n }\n\n const relatedTarget = {\n relatedTarget: this._element\n }\n\n this._completeHide(relatedTarget)\n }\n\n dispose() {\n if (this._popper) {\n this._popper.destroy()\n }\n\n super.dispose()\n }\n\n update() {\n this._inNavbar = this._detectNavbar()\n if (this._popper) {\n this._popper.update()\n }\n }\n\n // Private\n _completeHide(relatedTarget) {\n const hideEvent = EventHandler.trigger(this._element, EVENT_HIDE, relatedTarget)\n if (hideEvent.defaultPrevented) {\n return\n }\n\n // If this is a touch-enabled device we remove the extra\n // empty mouseover listeners we added for iOS support\n if ('ontouchstart' in document.documentElement) {\n for (const element of [].concat(...document.body.children)) {\n EventHandler.off(element, 'mouseover', noop)\n }\n }\n\n if (this._popper) {\n this._popper.destroy()\n }\n\n this._menu.classList.remove(CLASS_NAME_SHOW)\n this._element.classList.remove(CLASS_NAME_SHOW)\n this._element.setAttribute('aria-expanded', 'false')\n Manipulator.removeDataAttribute(this._menu, 'popper')\n EventHandler.trigger(this._element, EVENT_HIDDEN, relatedTarget)\n }\n\n _getConfig(config) {\n config = super._getConfig(config)\n\n if (typeof config.reference === 'object' && !isElement(config.reference) &&\n typeof config.reference.getBoundingClientRect !== 'function'\n ) {\n // Popper virtual elements require a getBoundingClientRect method\n throw new TypeError(`${NAME.toUpperCase()}: Option \"reference\" provided type \"object\" without a required \"getBoundingClientRect\" method.`)\n }\n\n return config\n }\n\n _createPopper() {\n if (typeof Popper === 'undefined') {\n throw new TypeError('Bootstrap\\'s dropdowns require Popper (https://popper.js.org)')\n }\n\n let referenceElement = this._element\n\n if (this._config.reference === 'parent') {\n referenceElement = this._parent\n } else if (isElement(this._config.reference)) {\n referenceElement = getElement(this._config.reference)\n } else if (typeof this._config.reference === 'object') {\n referenceElement = this._config.reference\n }\n\n const popperConfig = this._getPopperConfig()\n this._popper = Popper.createPopper(referenceElement, this._menu, popperConfig)\n }\n\n _isShown() {\n return this._menu.classList.contains(CLASS_NAME_SHOW)\n }\n\n _getPlacement() {\n const parentDropdown = this._parent\n\n if (parentDropdown.classList.contains(CLASS_NAME_DROPEND)) {\n return PLACEMENT_RIGHT\n }\n\n if (parentDropdown.classList.contains(CLASS_NAME_DROPSTART)) {\n return PLACEMENT_LEFT\n }\n\n if (parentDropdown.classList.contains(CLASS_NAME_DROPUP_CENTER)) {\n return PLACEMENT_TOPCENTER\n }\n\n if (parentDropdown.classList.contains(CLASS_NAME_DROPDOWN_CENTER)) {\n return PLACEMENT_BOTTOMCENTER\n }\n\n // We need to trim the value because custom properties can also include spaces\n const isEnd = getComputedStyle(this._menu).getPropertyValue('--bs-position').trim() === 'end'\n\n if (parentDropdown.classList.contains(CLASS_NAME_DROPUP)) {\n return isEnd ? PLACEMENT_TOPEND : PLACEMENT_TOP\n }\n\n return isEnd ? PLACEMENT_BOTTOMEND : PLACEMENT_BOTTOM\n }\n\n _detectNavbar() {\n return this._element.closest(SELECTOR_NAVBAR) !== null\n }\n\n _getOffset() {\n const { offset } = this._config\n\n if (typeof offset === 'string') {\n return offset.split(',').map(value => Number.parseInt(value, 10))\n }\n\n if (typeof offset === 'function') {\n return popperData => offset(popperData, this._element)\n }\n\n return offset\n }\n\n _getPopperConfig() {\n const defaultBsPopperConfig = {\n placement: this._getPlacement(),\n modifiers: [{\n name: 'preventOverflow',\n options: {\n boundary: this._config.boundary\n }\n },\n {\n name: 'offset',\n options: {\n offset: this._getOffset()\n }\n }]\n }\n\n // Disable Popper if we have a static display or Dropdown is in Navbar\n if (this._inNavbar || this._config.display === 'static') {\n Manipulator.setDataAttribute(this._menu, 'popper', 'static') // TODO: v6 remove\n defaultBsPopperConfig.modifiers = [{\n name: 'applyStyles',\n enabled: false\n }]\n }\n\n return {\n ...defaultBsPopperConfig,\n ...execute(this._config.popperConfig, [defaultBsPopperConfig])\n }\n }\n\n _selectMenuItem({ key, target }) {\n const items = SelectorEngine.find(SELECTOR_VISIBLE_ITEMS, this._menu).filter(element => isVisible(element))\n\n if (!items.length) {\n return\n }\n\n // if target isn't included in items (e.g. when expanding the dropdown)\n // allow cycling to get the last item in case key equals ARROW_UP_KEY\n getNextActiveElement(items, target, key === ARROW_DOWN_KEY, !items.includes(target)).focus()\n }\n\n // Static\n static jQueryInterface(config) {\n return this.each(function () {\n const data = Dropdown.getOrCreateInstance(this, config)\n\n if (typeof config !== 'string') {\n return\n }\n\n if (typeof data[config] === 'undefined') {\n throw new TypeError(`No method named \"${config}\"`)\n }\n\n data[config]()\n })\n }\n\n static clearMenus(event) {\n if (event.button === RIGHT_MOUSE_BUTTON || (event.type === 'keyup' && event.key !== TAB_KEY)) {\n return\n }\n\n const openToggles = SelectorEngine.find(SELECTOR_DATA_TOGGLE_SHOWN)\n\n for (const toggle of openToggles) {\n const context = Dropdown.getInstance(toggle)\n if (!context || context._config.autoClose === false) {\n continue\n }\n\n const composedPath = event.composedPath()\n const isMenuTarget = composedPath.includes(context._menu)\n if (\n composedPath.includes(context._element) ||\n (context._config.autoClose === 'inside' && !isMenuTarget) ||\n (context._config.autoClose === 'outside' && isMenuTarget)\n ) {\n continue\n }\n\n // Tab navigation through the dropdown menu or events from contained inputs shouldn't close the menu\n if (context._menu.contains(event.target) && ((event.type === 'keyup' && event.key === TAB_KEY) || /input|select|option|textarea|form/i.test(event.target.tagName))) {\n continue\n }\n\n const relatedTarget = { relatedTarget: context._element }\n\n if (event.type === 'click') {\n relatedTarget.clickEvent = event\n }\n\n context._completeHide(relatedTarget)\n }\n }\n\n static dataApiKeydownHandler(event) {\n // If not an UP | DOWN | ESCAPE key => not a dropdown command\n // If input/textarea && if key is other than ESCAPE => not a dropdown command\n\n const isInput = /input|textarea/i.test(event.target.tagName)\n const isEscapeEvent = event.key === ESCAPE_KEY\n const isUpOrDownEvent = [ARROW_UP_KEY, ARROW_DOWN_KEY].includes(event.key)\n\n if (!isUpOrDownEvent && !isEscapeEvent) {\n return\n }\n\n if (isInput && !isEscapeEvent) {\n return\n }\n\n event.preventDefault()\n\n // TODO: v6 revert #37011 & change markup https://getbootstrap.com/docs/5.3/forms/input-group/\n const getToggleButton = this.matches(SELECTOR_DATA_TOGGLE) ?\n this :\n (SelectorEngine.prev(this, SELECTOR_DATA_TOGGLE)[0] ||\n SelectorEngine.next(this, SELECTOR_DATA_TOGGLE)[0] ||\n SelectorEngine.findOne(SELECTOR_DATA_TOGGLE, event.delegateTarget.parentNode))\n\n const instance = Dropdown.getOrCreateInstance(getToggleButton)\n\n if (isUpOrDownEvent) {\n event.stopPropagation()\n instance.show()\n instance._selectMenuItem(event)\n return\n }\n\n if (instance._isShown()) { // else is escape and we check if it is shown\n event.stopPropagation()\n instance.hide()\n getToggleButton.focus()\n }\n }\n}\n\n/**\n * Data API implementation\n */\n\nEventHandler.on(document, EVENT_KEYDOWN_DATA_API, SELECTOR_DATA_TOGGLE, Dropdown.dataApiKeydownHandler)\nEventHandler.on(document, EVENT_KEYDOWN_DATA_API, SELECTOR_MENU, Dropdown.dataApiKeydownHandler)\nEventHandler.on(document, EVENT_CLICK_DATA_API, Dropdown.clearMenus)\nEventHandler.on(document, EVENT_KEYUP_DATA_API, Dropdown.clearMenus)\nEventHandler.on(document, EVENT_CLICK_DATA_API, SELECTOR_DATA_TOGGLE, function (event) {\n event.preventDefault()\n Dropdown.getOrCreateInstance(this).toggle()\n})\n\n/**\n * jQuery\n */\n\ndefineJQueryPlugin(Dropdown)\n\nexport default Dropdown\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap util/backdrop.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport EventHandler from '../dom/event-handler.js'\nimport Config from './config.js'\nimport { execute, executeAfterTransition, getElement, reflow } from './index.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'backdrop'\nconst CLASS_NAME_FADE = 'fade'\nconst CLASS_NAME_SHOW = 'show'\nconst EVENT_MOUSEDOWN = `mousedown.bs.${NAME}`\n\nconst Default = {\n className: 'modal-backdrop',\n clickCallback: null,\n isAnimated: false,\n isVisible: true, // if false, we use the backdrop helper without adding any element to the dom\n rootElement: 'body' // give the choice to place backdrop under different elements\n}\n\nconst DefaultType = {\n className: 'string',\n clickCallback: '(function|null)',\n isAnimated: 'boolean',\n isVisible: 'boolean',\n rootElement: '(element|string)'\n}\n\n/**\n * Class definition\n */\n\nclass Backdrop extends Config {\n constructor(config) {\n super()\n this._config = this._getConfig(config)\n this._isAppended = false\n this._element = null\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n show(callback) {\n if (!this._config.isVisible) {\n execute(callback)\n return\n }\n\n this._append()\n\n const element = this._getElement()\n if (this._config.isAnimated) {\n reflow(element)\n }\n\n element.classList.add(CLASS_NAME_SHOW)\n\n this._emulateAnimation(() => {\n execute(callback)\n })\n }\n\n hide(callback) {\n if (!this._config.isVisible) {\n execute(callback)\n return\n }\n\n this._getElement().classList.remove(CLASS_NAME_SHOW)\n\n this._emulateAnimation(() => {\n this.dispose()\n execute(callback)\n })\n }\n\n dispose() {\n if (!this._isAppended) {\n return\n }\n\n EventHandler.off(this._element, EVENT_MOUSEDOWN)\n\n this._element.remove()\n this._isAppended = false\n }\n\n // Private\n _getElement() {\n if (!this._element) {\n const backdrop = document.createElement('div')\n backdrop.className = this._config.className\n if (this._config.isAnimated) {\n backdrop.classList.add(CLASS_NAME_FADE)\n }\n\n this._element = backdrop\n }\n\n return this._element\n }\n\n _configAfterMerge(config) {\n // use getElement() with the default \"body\" to get a fresh Element on each instantiation\n config.rootElement = getElement(config.rootElement)\n return config\n }\n\n _append() {\n if (this._isAppended) {\n return\n }\n\n const element = this._getElement()\n this._config.rootElement.append(element)\n\n EventHandler.on(element, EVENT_MOUSEDOWN, () => {\n execute(this._config.clickCallback)\n })\n\n this._isAppended = true\n }\n\n _emulateAnimation(callback) {\n executeAfterTransition(callback, this._getElement(), this._config.isAnimated)\n }\n}\n\nexport default Backdrop\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap util/focustrap.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport EventHandler from '../dom/event-handler.js'\nimport SelectorEngine from '../dom/selector-engine.js'\nimport Config from './config.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'focustrap'\nconst DATA_KEY = 'bs.focustrap'\nconst EVENT_KEY = `.${DATA_KEY}`\nconst EVENT_FOCUSIN = `focusin${EVENT_KEY}`\nconst EVENT_KEYDOWN_TAB = `keydown.tab${EVENT_KEY}`\n\nconst TAB_KEY = 'Tab'\nconst TAB_NAV_FORWARD = 'forward'\nconst TAB_NAV_BACKWARD = 'backward'\n\nconst Default = {\n autofocus: true,\n trapElement: null // The element to trap focus inside of\n}\n\nconst DefaultType = {\n autofocus: 'boolean',\n trapElement: 'element'\n}\n\n/**\n * Class definition\n */\n\nclass FocusTrap extends Config {\n constructor(config) {\n super()\n this._config = this._getConfig(config)\n this._isActive = false\n this._lastTabNavDirection = null\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n activate() {\n if (this._isActive) {\n return\n }\n\n if (this._config.autofocus) {\n this._config.trapElement.focus()\n }\n\n EventHandler.off(document, EVENT_KEY) // guard against infinite focus loop\n EventHandler.on(document, EVENT_FOCUSIN, event => this._handleFocusin(event))\n EventHandler.on(document, EVENT_KEYDOWN_TAB, event => this._handleKeydown(event))\n\n this._isActive = true\n }\n\n deactivate() {\n if (!this._isActive) {\n return\n }\n\n this._isActive = false\n EventHandler.off(document, EVENT_KEY)\n }\n\n // Private\n _handleFocusin(event) {\n const { trapElement } = this._config\n\n if (event.target === document || event.target === trapElement || trapElement.contains(event.target)) {\n return\n }\n\n const elements = SelectorEngine.focusableChildren(trapElement)\n\n if (elements.length === 0) {\n trapElement.focus()\n } else if (this._lastTabNavDirection === TAB_NAV_BACKWARD) {\n elements[elements.length - 1].focus()\n } else {\n elements[0].focus()\n }\n }\n\n _handleKeydown(event) {\n if (event.key !== TAB_KEY) {\n return\n }\n\n this._lastTabNavDirection = event.shiftKey ? TAB_NAV_BACKWARD : TAB_NAV_FORWARD\n }\n}\n\nexport default FocusTrap\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap util/scrollBar.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport Manipulator from '../dom/manipulator.js'\nimport SelectorEngine from '../dom/selector-engine.js'\nimport { isElement } from './index.js'\n\n/**\n * Constants\n */\n\nconst SELECTOR_FIXED_CONTENT = '.fixed-top, .fixed-bottom, .is-fixed, .sticky-top'\nconst SELECTOR_STICKY_CONTENT = '.sticky-top'\nconst PROPERTY_PADDING = 'padding-right'\nconst PROPERTY_MARGIN = 'margin-right'\n\n/**\n * Class definition\n */\n\nclass ScrollBarHelper {\n constructor() {\n this._element = document.body\n }\n\n // Public\n getWidth() {\n // https://developer.mozilla.org/en-US/docs/Web/API/Window/innerWidth#usage_notes\n const documentWidth = document.documentElement.clientWidth\n return Math.abs(window.innerWidth - documentWidth)\n }\n\n hide() {\n const width = this.getWidth()\n this._disableOverFlow()\n // give padding to element to balance the hidden scrollbar width\n this._setElementAttributes(this._element, PROPERTY_PADDING, calculatedValue => calculatedValue + width)\n // trick: We adjust positive paddingRight and negative marginRight to sticky-top elements to keep showing fullwidth\n this._setElementAttributes(SELECTOR_FIXED_CONTENT, PROPERTY_PADDING, calculatedValue => calculatedValue + width)\n this._setElementAttributes(SELECTOR_STICKY_CONTENT, PROPERTY_MARGIN, calculatedValue => calculatedValue - width)\n }\n\n reset() {\n this._resetElementAttributes(this._element, 'overflow')\n this._resetElementAttributes(this._element, PROPERTY_PADDING)\n this._resetElementAttributes(SELECTOR_FIXED_CONTENT, PROPERTY_PADDING)\n this._resetElementAttributes(SELECTOR_STICKY_CONTENT, PROPERTY_MARGIN)\n }\n\n isOverflowing() {\n return this.getWidth() > 0\n }\n\n // Private\n _disableOverFlow() {\n this._saveInitialAttribute(this._element, 'overflow')\n this._element.style.overflow = 'hidden'\n }\n\n _setElementAttributes(selector, styleProperty, callback) {\n const scrollbarWidth = this.getWidth()\n const manipulationCallBack = element => {\n if (element !== this._element && window.innerWidth > element.clientWidth + scrollbarWidth) {\n return\n }\n\n this._saveInitialAttribute(element, styleProperty)\n const calculatedValue = window.getComputedStyle(element).getPropertyValue(styleProperty)\n element.style.setProperty(styleProperty, `${callback(Number.parseFloat(calculatedValue))}px`)\n }\n\n this._applyManipulationCallback(selector, manipulationCallBack)\n }\n\n _saveInitialAttribute(element, styleProperty) {\n const actualValue = element.style.getPropertyValue(styleProperty)\n if (actualValue) {\n Manipulator.setDataAttribute(element, styleProperty, actualValue)\n }\n }\n\n _resetElementAttributes(selector, styleProperty) {\n const manipulationCallBack = element => {\n const value = Manipulator.getDataAttribute(element, styleProperty)\n // We only want to remove the property if the value is `null`; the value can also be zero\n if (value === null) {\n element.style.removeProperty(styleProperty)\n return\n }\n\n Manipulator.removeDataAttribute(element, styleProperty)\n element.style.setProperty(styleProperty, value)\n }\n\n this._applyManipulationCallback(selector, manipulationCallBack)\n }\n\n _applyManipulationCallback(selector, callBack) {\n if (isElement(selector)) {\n callBack(selector)\n return\n }\n\n for (const sel of SelectorEngine.find(selector, this._element)) {\n callBack(sel)\n }\n }\n}\n\nexport default ScrollBarHelper\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap modal.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport BaseComponent from './base-component.js'\nimport EventHandler from './dom/event-handler.js'\nimport SelectorEngine from './dom/selector-engine.js'\nimport Backdrop from './util/backdrop.js'\nimport { enableDismissTrigger } from './util/component-functions.js'\nimport FocusTrap from './util/focustrap.js'\nimport { defineJQueryPlugin, isRTL, isVisible, reflow } from './util/index.js'\nimport ScrollBarHelper from './util/scrollbar.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'modal'\nconst DATA_KEY = 'bs.modal'\nconst EVENT_KEY = `.${DATA_KEY}`\nconst DATA_API_KEY = '.data-api'\nconst ESCAPE_KEY = 'Escape'\n\nconst EVENT_HIDE = `hide${EVENT_KEY}`\nconst EVENT_HIDE_PREVENTED = `hidePrevented${EVENT_KEY}`\nconst EVENT_HIDDEN = `hidden${EVENT_KEY}`\nconst EVENT_SHOW = `show${EVENT_KEY}`\nconst EVENT_SHOWN = `shown${EVENT_KEY}`\nconst EVENT_RESIZE = `resize${EVENT_KEY}`\nconst EVENT_CLICK_DISMISS = `click.dismiss${EVENT_KEY}`\nconst EVENT_MOUSEDOWN_DISMISS = `mousedown.dismiss${EVENT_KEY}`\nconst EVENT_KEYDOWN_DISMISS = `keydown.dismiss${EVENT_KEY}`\nconst EVENT_CLICK_DATA_API = `click${EVENT_KEY}${DATA_API_KEY}`\n\nconst CLASS_NAME_OPEN = 'modal-open'\nconst CLASS_NAME_FADE = 'fade'\nconst CLASS_NAME_SHOW = 'show'\nconst CLASS_NAME_STATIC = 'modal-static'\n\nconst OPEN_SELECTOR = '.modal.show'\nconst SELECTOR_DIALOG = '.modal-dialog'\nconst SELECTOR_MODAL_BODY = '.modal-body'\nconst SELECTOR_DATA_TOGGLE = '[data-bs-toggle=\"modal\"]'\n\nconst Default = {\n backdrop: true,\n focus: true,\n keyboard: true\n}\n\nconst DefaultType = {\n backdrop: '(boolean|string)',\n focus: 'boolean',\n keyboard: 'boolean'\n}\n\n/**\n * Class definition\n */\n\nclass Modal extends BaseComponent {\n constructor(element, config) {\n super(element, config)\n\n this._dialog = SelectorEngine.findOne(SELECTOR_DIALOG, this._element)\n this._backdrop = this._initializeBackDrop()\n this._focustrap = this._initializeFocusTrap()\n this._isShown = false\n this._isTransitioning = false\n this._scrollBar = new ScrollBarHelper()\n\n this._addEventListeners()\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n toggle(relatedTarget) {\n return this._isShown ? this.hide() : this.show(relatedTarget)\n }\n\n show(relatedTarget) {\n if (this._isShown || this._isTransitioning) {\n return\n }\n\n const showEvent = EventHandler.trigger(this._element, EVENT_SHOW, {\n relatedTarget\n })\n\n if (showEvent.defaultPrevented) {\n return\n }\n\n this._isShown = true\n this._isTransitioning = true\n\n this._scrollBar.hide()\n\n document.body.classList.add(CLASS_NAME_OPEN)\n\n this._adjustDialog()\n\n this._backdrop.show(() => this._showElement(relatedTarget))\n }\n\n hide() {\n if (!this._isShown || this._isTransitioning) {\n return\n }\n\n const hideEvent = EventHandler.trigger(this._element, EVENT_HIDE)\n\n if (hideEvent.defaultPrevented) {\n return\n }\n\n this._isShown = false\n this._isTransitioning = true\n this._focustrap.deactivate()\n\n this._element.classList.remove(CLASS_NAME_SHOW)\n\n this._queueCallback(() => this._hideModal(), this._element, this._isAnimated())\n }\n\n dispose() {\n EventHandler.off(window, EVENT_KEY)\n EventHandler.off(this._dialog, EVENT_KEY)\n\n this._backdrop.dispose()\n this._focustrap.deactivate()\n\n super.dispose()\n }\n\n handleUpdate() {\n this._adjustDialog()\n }\n\n // Private\n _initializeBackDrop() {\n return new Backdrop({\n isVisible: Boolean(this._config.backdrop), // 'static' option will be translated to true, and booleans will keep their value,\n isAnimated: this._isAnimated()\n })\n }\n\n _initializeFocusTrap() {\n return new FocusTrap({\n trapElement: this._element\n })\n }\n\n _showElement(relatedTarget) {\n // try to append dynamic modal\n if (!document.body.contains(this._element)) {\n document.body.append(this._element)\n }\n\n this._element.style.display = 'block'\n this._element.removeAttribute('aria-hidden')\n this._element.setAttribute('aria-modal', true)\n this._element.setAttribute('role', 'dialog')\n this._element.scrollTop = 0\n\n const modalBody = SelectorEngine.findOne(SELECTOR_MODAL_BODY, this._dialog)\n if (modalBody) {\n modalBody.scrollTop = 0\n }\n\n reflow(this._element)\n\n this._element.classList.add(CLASS_NAME_SHOW)\n\n const transitionComplete = () => {\n if (this._config.focus) {\n this._focustrap.activate()\n }\n\n this._isTransitioning = false\n EventHandler.trigger(this._element, EVENT_SHOWN, {\n relatedTarget\n })\n }\n\n this._queueCallback(transitionComplete, this._dialog, this._isAnimated())\n }\n\n _addEventListeners() {\n EventHandler.on(this._element, EVENT_KEYDOWN_DISMISS, event => {\n if (event.key !== ESCAPE_KEY) {\n return\n }\n\n if (this._config.keyboard) {\n this.hide()\n return\n }\n\n this._triggerBackdropTransition()\n })\n\n EventHandler.on(window, EVENT_RESIZE, () => {\n if (this._isShown && !this._isTransitioning) {\n this._adjustDialog()\n }\n })\n\n EventHandler.on(this._element, EVENT_MOUSEDOWN_DISMISS, event => {\n // a bad trick to segregate clicks that may start inside dialog but end outside, and avoid listen to scrollbar clicks\n EventHandler.one(this._element, EVENT_CLICK_DISMISS, event2 => {\n if (this._element !== event.target || this._element !== event2.target) {\n return\n }\n\n if (this._config.backdrop === 'static') {\n this._triggerBackdropTransition()\n return\n }\n\n if (this._config.backdrop) {\n this.hide()\n }\n })\n })\n }\n\n _hideModal() {\n this._element.style.display = 'none'\n this._element.setAttribute('aria-hidden', true)\n this._element.removeAttribute('aria-modal')\n this._element.removeAttribute('role')\n this._isTransitioning = false\n\n this._backdrop.hide(() => {\n document.body.classList.remove(CLASS_NAME_OPEN)\n this._resetAdjustments()\n this._scrollBar.reset()\n EventHandler.trigger(this._element, EVENT_HIDDEN)\n })\n }\n\n _isAnimated() {\n return this._element.classList.contains(CLASS_NAME_FADE)\n }\n\n _triggerBackdropTransition() {\n const hideEvent = EventHandler.trigger(this._element, EVENT_HIDE_PREVENTED)\n if (hideEvent.defaultPrevented) {\n return\n }\n\n const isModalOverflowing = this._element.scrollHeight > document.documentElement.clientHeight\n const initialOverflowY = this._element.style.overflowY\n // return if the following background transition hasn't yet completed\n if (initialOverflowY === 'hidden' || this._element.classList.contains(CLASS_NAME_STATIC)) {\n return\n }\n\n if (!isModalOverflowing) {\n this._element.style.overflowY = 'hidden'\n }\n\n this._element.classList.add(CLASS_NAME_STATIC)\n this._queueCallback(() => {\n this._element.classList.remove(CLASS_NAME_STATIC)\n this._queueCallback(() => {\n this._element.style.overflowY = initialOverflowY\n }, this._dialog)\n }, this._dialog)\n\n this._element.focus()\n }\n\n /**\n * The following methods are used to handle overflowing modals\n */\n\n _adjustDialog() {\n const isModalOverflowing = this._element.scrollHeight > document.documentElement.clientHeight\n const scrollbarWidth = this._scrollBar.getWidth()\n const isBodyOverflowing = scrollbarWidth > 0\n\n if (isBodyOverflowing && !isModalOverflowing) {\n const property = isRTL() ? 'paddingLeft' : 'paddingRight'\n this._element.style[property] = `${scrollbarWidth}px`\n }\n\n if (!isBodyOverflowing && isModalOverflowing) {\n const property = isRTL() ? 'paddingRight' : 'paddingLeft'\n this._element.style[property] = `${scrollbarWidth}px`\n }\n }\n\n _resetAdjustments() {\n this._element.style.paddingLeft = ''\n this._element.style.paddingRight = ''\n }\n\n // Static\n static jQueryInterface(config, relatedTarget) {\n return this.each(function () {\n const data = Modal.getOrCreateInstance(this, config)\n\n if (typeof config !== 'string') {\n return\n }\n\n if (typeof data[config] === 'undefined') {\n throw new TypeError(`No method named \"${config}\"`)\n }\n\n data[config](relatedTarget)\n })\n }\n}\n\n/**\n * Data API implementation\n */\n\nEventHandler.on(document, EVENT_CLICK_DATA_API, SELECTOR_DATA_TOGGLE, function (event) {\n const target = SelectorEngine.getElementFromSelector(this)\n\n if (['A', 'AREA'].includes(this.tagName)) {\n event.preventDefault()\n }\n\n EventHandler.one(target, EVENT_SHOW, showEvent => {\n if (showEvent.defaultPrevented) {\n // only register focus restorer if modal will actually get shown\n return\n }\n\n EventHandler.one(target, EVENT_HIDDEN, () => {\n if (isVisible(this)) {\n this.focus()\n }\n })\n })\n\n // avoid conflict when clicking modal toggler while another one is open\n const alreadyOpen = SelectorEngine.findOne(OPEN_SELECTOR)\n if (alreadyOpen) {\n Modal.getInstance(alreadyOpen).hide()\n }\n\n const data = Modal.getOrCreateInstance(target)\n\n data.toggle(this)\n})\n\nenableDismissTrigger(Modal)\n\n/**\n * jQuery\n */\n\ndefineJQueryPlugin(Modal)\n\nexport default Modal\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap offcanvas.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport BaseComponent from './base-component.js'\nimport EventHandler from './dom/event-handler.js'\nimport SelectorEngine from './dom/selector-engine.js'\nimport Backdrop from './util/backdrop.js'\nimport { enableDismissTrigger } from './util/component-functions.js'\nimport FocusTrap from './util/focustrap.js'\nimport {\n defineJQueryPlugin,\n isDisabled,\n isVisible\n} from './util/index.js'\nimport ScrollBarHelper from './util/scrollbar.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'offcanvas'\nconst DATA_KEY = 'bs.offcanvas'\nconst EVENT_KEY = `.${DATA_KEY}`\nconst DATA_API_KEY = '.data-api'\nconst EVENT_LOAD_DATA_API = `load${EVENT_KEY}${DATA_API_KEY}`\nconst ESCAPE_KEY = 'Escape'\n\nconst CLASS_NAME_SHOW = 'show'\nconst CLASS_NAME_SHOWING = 'showing'\nconst CLASS_NAME_HIDING = 'hiding'\nconst CLASS_NAME_BACKDROP = 'offcanvas-backdrop'\nconst OPEN_SELECTOR = '.offcanvas.show'\n\nconst EVENT_SHOW = `show${EVENT_KEY}`\nconst EVENT_SHOWN = `shown${EVENT_KEY}`\nconst EVENT_HIDE = `hide${EVENT_KEY}`\nconst EVENT_HIDE_PREVENTED = `hidePrevented${EVENT_KEY}`\nconst EVENT_HIDDEN = `hidden${EVENT_KEY}`\nconst EVENT_RESIZE = `resize${EVENT_KEY}`\nconst EVENT_CLICK_DATA_API = `click${EVENT_KEY}${DATA_API_KEY}`\nconst EVENT_KEYDOWN_DISMISS = `keydown.dismiss${EVENT_KEY}`\n\nconst SELECTOR_DATA_TOGGLE = '[data-bs-toggle=\"offcanvas\"]'\n\nconst Default = {\n backdrop: true,\n keyboard: true,\n scroll: false\n}\n\nconst DefaultType = {\n backdrop: '(boolean|string)',\n keyboard: 'boolean',\n scroll: 'boolean'\n}\n\n/**\n * Class definition\n */\n\nclass Offcanvas extends BaseComponent {\n constructor(element, config) {\n super(element, config)\n\n this._isShown = false\n this._backdrop = this._initializeBackDrop()\n this._focustrap = this._initializeFocusTrap()\n this._addEventListeners()\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n toggle(relatedTarget) {\n return this._isShown ? this.hide() : this.show(relatedTarget)\n }\n\n show(relatedTarget) {\n if (this._isShown) {\n return\n }\n\n const showEvent = EventHandler.trigger(this._element, EVENT_SHOW, { relatedTarget })\n\n if (showEvent.defaultPrevented) {\n return\n }\n\n this._isShown = true\n this._backdrop.show()\n\n if (!this._config.scroll) {\n new ScrollBarHelper().hide()\n }\n\n this._element.setAttribute('aria-modal', true)\n this._element.setAttribute('role', 'dialog')\n this._element.classList.add(CLASS_NAME_SHOWING)\n\n const completeCallBack = () => {\n if (!this._config.scroll || this._config.backdrop) {\n this._focustrap.activate()\n }\n\n this._element.classList.add(CLASS_NAME_SHOW)\n this._element.classList.remove(CLASS_NAME_SHOWING)\n EventHandler.trigger(this._element, EVENT_SHOWN, { relatedTarget })\n }\n\n this._queueCallback(completeCallBack, this._element, true)\n }\n\n hide() {\n if (!this._isShown) {\n return\n }\n\n const hideEvent = EventHandler.trigger(this._element, EVENT_HIDE)\n\n if (hideEvent.defaultPrevented) {\n return\n }\n\n this._focustrap.deactivate()\n this._element.blur()\n this._isShown = false\n this._element.classList.add(CLASS_NAME_HIDING)\n this._backdrop.hide()\n\n const completeCallback = () => {\n this._element.classList.remove(CLASS_NAME_SHOW, CLASS_NAME_HIDING)\n this._element.removeAttribute('aria-modal')\n this._element.removeAttribute('role')\n\n if (!this._config.scroll) {\n new ScrollBarHelper().reset()\n }\n\n EventHandler.trigger(this._element, EVENT_HIDDEN)\n }\n\n this._queueCallback(completeCallback, this._element, true)\n }\n\n dispose() {\n this._backdrop.dispose()\n this._focustrap.deactivate()\n super.dispose()\n }\n\n // Private\n _initializeBackDrop() {\n const clickCallback = () => {\n if (this._config.backdrop === 'static') {\n EventHandler.trigger(this._element, EVENT_HIDE_PREVENTED)\n return\n }\n\n this.hide()\n }\n\n // 'static' option will be translated to true, and booleans will keep their value\n const isVisible = Boolean(this._config.backdrop)\n\n return new Backdrop({\n className: CLASS_NAME_BACKDROP,\n isVisible,\n isAnimated: true,\n rootElement: this._element.parentNode,\n clickCallback: isVisible ? clickCallback : null\n })\n }\n\n _initializeFocusTrap() {\n return new FocusTrap({\n trapElement: this._element\n })\n }\n\n _addEventListeners() {\n EventHandler.on(this._element, EVENT_KEYDOWN_DISMISS, event => {\n if (event.key !== ESCAPE_KEY) {\n return\n }\n\n if (this._config.keyboard) {\n this.hide()\n return\n }\n\n EventHandler.trigger(this._element, EVENT_HIDE_PREVENTED)\n })\n }\n\n // Static\n static jQueryInterface(config) {\n return this.each(function () {\n const data = Offcanvas.getOrCreateInstance(this, config)\n\n if (typeof config !== 'string') {\n return\n }\n\n if (data[config] === undefined || config.startsWith('_') || config === 'constructor') {\n throw new TypeError(`No method named \"${config}\"`)\n }\n\n data[config](this)\n })\n }\n}\n\n/**\n * Data API implementation\n */\n\nEventHandler.on(document, EVENT_CLICK_DATA_API, SELECTOR_DATA_TOGGLE, function (event) {\n const target = SelectorEngine.getElementFromSelector(this)\n\n if (['A', 'AREA'].includes(this.tagName)) {\n event.preventDefault()\n }\n\n if (isDisabled(this)) {\n return\n }\n\n EventHandler.one(target, EVENT_HIDDEN, () => {\n // focus on trigger when it is closed\n if (isVisible(this)) {\n this.focus()\n }\n })\n\n // avoid conflict when clicking a toggler of an offcanvas, while another is open\n const alreadyOpen = SelectorEngine.findOne(OPEN_SELECTOR)\n if (alreadyOpen && alreadyOpen !== target) {\n Offcanvas.getInstance(alreadyOpen).hide()\n }\n\n const data = Offcanvas.getOrCreateInstance(target)\n data.toggle(this)\n})\n\nEventHandler.on(window, EVENT_LOAD_DATA_API, () => {\n for (const selector of SelectorEngine.find(OPEN_SELECTOR)) {\n Offcanvas.getOrCreateInstance(selector).show()\n }\n})\n\nEventHandler.on(window, EVENT_RESIZE, () => {\n for (const element of SelectorEngine.find('[aria-modal][class*=show][class*=offcanvas-]')) {\n if (getComputedStyle(element).position !== 'fixed') {\n Offcanvas.getOrCreateInstance(element).hide()\n }\n }\n})\n\nenableDismissTrigger(Offcanvas)\n\n/**\n * jQuery\n */\n\ndefineJQueryPlugin(Offcanvas)\n\nexport default Offcanvas\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap util/sanitizer.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\n// js-docs-start allow-list\nconst ARIA_ATTRIBUTE_PATTERN = /^aria-[\\w-]*$/i\n\nexport const DefaultAllowlist = {\n // Global attributes allowed on any supplied element below.\n '*': ['class', 'dir', 'id', 'lang', 'role', ARIA_ATTRIBUTE_PATTERN],\n a: ['target', 'href', 'title', 'rel'],\n area: [],\n b: [],\n br: [],\n col: [],\n code: [],\n div: [],\n em: [],\n hr: [],\n h1: [],\n h2: [],\n h3: [],\n h4: [],\n h5: [],\n h6: [],\n i: [],\n img: ['src', 'srcset', 'alt', 'title', 'width', 'height'],\n li: [],\n ol: [],\n p: [],\n pre: [],\n s: [],\n small: [],\n span: [],\n sub: [],\n sup: [],\n strong: [],\n u: [],\n ul: []\n}\n// js-docs-end allow-list\n\nconst uriAttributes = new Set([\n 'background',\n 'cite',\n 'href',\n 'itemtype',\n 'longdesc',\n 'poster',\n 'src',\n 'xlink:href'\n])\n\n/**\n * A pattern that recognizes URLs that are safe wrt. XSS in URL navigation\n * contexts.\n *\n * Shout-out to Angular https://github.com/angular/angular/blob/15.2.8/packages/core/src/sanitization/url_sanitizer.ts#L38\n */\n// eslint-disable-next-line unicorn/better-regex\nconst SAFE_URL_PATTERN = /^(?!javascript:)(?:[a-z0-9+.-]+:|[^&:/?#]*(?:[/?#]|$))/i\n\nconst allowedAttribute = (attribute, allowedAttributeList) => {\n const attributeName = attribute.nodeName.toLowerCase()\n\n if (allowedAttributeList.includes(attributeName)) {\n if (uriAttributes.has(attributeName)) {\n return Boolean(SAFE_URL_PATTERN.test(attribute.nodeValue))\n }\n\n return true\n }\n\n // Check if a regular expression validates the attribute.\n return allowedAttributeList.filter(attributeRegex => attributeRegex instanceof RegExp)\n .some(regex => regex.test(attributeName))\n}\n\nexport function sanitizeHtml(unsafeHtml, allowList, sanitizeFunction) {\n if (!unsafeHtml.length) {\n return unsafeHtml\n }\n\n if (sanitizeFunction && typeof sanitizeFunction === 'function') {\n return sanitizeFunction(unsafeHtml)\n }\n\n const domParser = new window.DOMParser()\n const createdDocument = domParser.parseFromString(unsafeHtml, 'text/html')\n const elements = [].concat(...createdDocument.body.querySelectorAll('*'))\n\n for (const element of elements) {\n const elementName = element.nodeName.toLowerCase()\n\n if (!Object.keys(allowList).includes(elementName)) {\n element.remove()\n continue\n }\n\n const attributeList = [].concat(...element.attributes)\n const allowedAttributes = [].concat(allowList['*'] || [], allowList[elementName] || [])\n\n for (const attribute of attributeList) {\n if (!allowedAttribute(attribute, allowedAttributes)) {\n element.removeAttribute(attribute.nodeName)\n }\n }\n }\n\n return createdDocument.body.innerHTML\n}\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap util/template-factory.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport SelectorEngine from '../dom/selector-engine.js'\nimport Config from './config.js'\nimport { DefaultAllowlist, sanitizeHtml } from './sanitizer.js'\nimport { execute, getElement, isElement } from './index.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'TemplateFactory'\n\nconst Default = {\n allowList: DefaultAllowlist,\n content: {}, // { selector : text , selector2 : text2 , }\n extraClass: '',\n html: false,\n sanitize: true,\n sanitizeFn: null,\n template: ''\n}\n\nconst DefaultType = {\n allowList: 'object',\n content: 'object',\n extraClass: '(string|function)',\n html: 'boolean',\n sanitize: 'boolean',\n sanitizeFn: '(null|function)',\n template: 'string'\n}\n\nconst DefaultContentType = {\n entry: '(string|element|function|null)',\n selector: '(string|element)'\n}\n\n/**\n * Class definition\n */\n\nclass TemplateFactory extends Config {\n constructor(config) {\n super()\n this._config = this._getConfig(config)\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n getContent() {\n return Object.values(this._config.content)\n .map(config => this._resolvePossibleFunction(config))\n .filter(Boolean)\n }\n\n hasContent() {\n return this.getContent().length > 0\n }\n\n changeContent(content) {\n this._checkContent(content)\n this._config.content = { ...this._config.content, ...content }\n return this\n }\n\n toHtml() {\n const templateWrapper = document.createElement('div')\n templateWrapper.innerHTML = this._maybeSanitize(this._config.template)\n\n for (const [selector, text] of Object.entries(this._config.content)) {\n this._setContent(templateWrapper, text, selector)\n }\n\n const template = templateWrapper.children[0]\n const extraClass = this._resolvePossibleFunction(this._config.extraClass)\n\n if (extraClass) {\n template.classList.add(...extraClass.split(' '))\n }\n\n return template\n }\n\n // Private\n _typeCheckConfig(config) {\n super._typeCheckConfig(config)\n this._checkContent(config.content)\n }\n\n _checkContent(arg) {\n for (const [selector, content] of Object.entries(arg)) {\n super._typeCheckConfig({ selector, entry: content }, DefaultContentType)\n }\n }\n\n _setContent(template, content, selector) {\n const templateElement = SelectorEngine.findOne(selector, template)\n\n if (!templateElement) {\n return\n }\n\n content = this._resolvePossibleFunction(content)\n\n if (!content) {\n templateElement.remove()\n return\n }\n\n if (isElement(content)) {\n this._putElementInTemplate(getElement(content), templateElement)\n return\n }\n\n if (this._config.html) {\n templateElement.innerHTML = this._maybeSanitize(content)\n return\n }\n\n templateElement.textContent = content\n }\n\n _maybeSanitize(arg) {\n return this._config.sanitize ? sanitizeHtml(arg, this._config.allowList, this._config.sanitizeFn) : arg\n }\n\n _resolvePossibleFunction(arg) {\n return execute(arg, [this])\n }\n\n _putElementInTemplate(element, templateElement) {\n if (this._config.html) {\n templateElement.innerHTML = ''\n templateElement.append(element)\n return\n }\n\n templateElement.textContent = element.textContent\n }\n}\n\nexport default TemplateFactory\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap tooltip.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport * as Popper from '@popperjs/core'\nimport BaseComponent from './base-component.js'\nimport EventHandler from './dom/event-handler.js'\nimport Manipulator from './dom/manipulator.js'\nimport { defineJQueryPlugin, execute, findShadowRoot, getElement, getUID, isRTL, noop } from './util/index.js'\nimport { DefaultAllowlist } from './util/sanitizer.js'\nimport TemplateFactory from './util/template-factory.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'tooltip'\nconst DISALLOWED_ATTRIBUTES = new Set(['sanitize', 'allowList', 'sanitizeFn'])\n\nconst CLASS_NAME_FADE = 'fade'\nconst CLASS_NAME_MODAL = 'modal'\nconst CLASS_NAME_SHOW = 'show'\n\nconst SELECTOR_TOOLTIP_INNER = '.tooltip-inner'\nconst SELECTOR_MODAL = `.${CLASS_NAME_MODAL}`\n\nconst EVENT_MODAL_HIDE = 'hide.bs.modal'\n\nconst TRIGGER_HOVER = 'hover'\nconst TRIGGER_FOCUS = 'focus'\nconst TRIGGER_CLICK = 'click'\nconst TRIGGER_MANUAL = 'manual'\n\nconst EVENT_HIDE = 'hide'\nconst EVENT_HIDDEN = 'hidden'\nconst EVENT_SHOW = 'show'\nconst EVENT_SHOWN = 'shown'\nconst EVENT_INSERTED = 'inserted'\nconst EVENT_CLICK = 'click'\nconst EVENT_FOCUSIN = 'focusin'\nconst EVENT_FOCUSOUT = 'focusout'\nconst EVENT_MOUSEENTER = 'mouseenter'\nconst EVENT_MOUSELEAVE = 'mouseleave'\n\nconst AttachmentMap = {\n AUTO: 'auto',\n TOP: 'top',\n RIGHT: isRTL() ? 'left' : 'right',\n BOTTOM: 'bottom',\n LEFT: isRTL() ? 'right' : 'left'\n}\n\nconst Default = {\n allowList: DefaultAllowlist,\n animation: true,\n boundary: 'clippingParents',\n container: false,\n customClass: '',\n delay: 0,\n fallbackPlacements: ['top', 'right', 'bottom', 'left'],\n html: false,\n offset: [0, 6],\n placement: 'top',\n popperConfig: null,\n sanitize: true,\n sanitizeFn: null,\n selector: false,\n template: '
' +\n '' +\n '' +\n '
',\n title: '',\n trigger: 'hover focus'\n}\n\nconst DefaultType = {\n allowList: 'object',\n animation: 'boolean',\n boundary: '(string|element)',\n container: '(string|element|boolean)',\n customClass: '(string|function)',\n delay: '(number|object)',\n fallbackPlacements: 'array',\n html: 'boolean',\n offset: '(array|string|function)',\n placement: '(string|function)',\n popperConfig: '(null|object|function)',\n sanitize: 'boolean',\n sanitizeFn: '(null|function)',\n selector: '(string|boolean)',\n template: 'string',\n title: '(string|element|function)',\n trigger: 'string'\n}\n\n/**\n * Class definition\n */\n\nclass Tooltip extends BaseComponent {\n constructor(element, config) {\n if (typeof Popper === 'undefined') {\n throw new TypeError('Bootstrap\\'s tooltips require Popper (https://popper.js.org)')\n }\n\n super(element, config)\n\n // Private\n this._isEnabled = true\n this._timeout = 0\n this._isHovered = null\n this._activeTrigger = {}\n this._popper = null\n this._templateFactory = null\n this._newContent = null\n\n // Protected\n this.tip = null\n\n this._setListeners()\n\n if (!this._config.selector) {\n this._fixTitle()\n }\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n enable() {\n this._isEnabled = true\n }\n\n disable() {\n this._isEnabled = false\n }\n\n toggleEnabled() {\n this._isEnabled = !this._isEnabled\n }\n\n toggle() {\n if (!this._isEnabled) {\n return\n }\n\n this._activeTrigger.click = !this._activeTrigger.click\n if (this._isShown()) {\n this._leave()\n return\n }\n\n this._enter()\n }\n\n dispose() {\n clearTimeout(this._timeout)\n\n EventHandler.off(this._element.closest(SELECTOR_MODAL), EVENT_MODAL_HIDE, this._hideModalHandler)\n\n if (this._element.getAttribute('data-bs-original-title')) {\n this._element.setAttribute('title', this._element.getAttribute('data-bs-original-title'))\n }\n\n this._disposePopper()\n super.dispose()\n }\n\n show() {\n if (this._element.style.display === 'none') {\n throw new Error('Please use show on visible elements')\n }\n\n if (!(this._isWithContent() && this._isEnabled)) {\n return\n }\n\n const showEvent = EventHandler.trigger(this._element, this.constructor.eventName(EVENT_SHOW))\n const shadowRoot = findShadowRoot(this._element)\n const isInTheDom = (shadowRoot || this._element.ownerDocument.documentElement).contains(this._element)\n\n if (showEvent.defaultPrevented || !isInTheDom) {\n return\n }\n\n // TODO: v6 remove this or make it optional\n this._disposePopper()\n\n const tip = this._getTipElement()\n\n this._element.setAttribute('aria-describedby', tip.getAttribute('id'))\n\n const { container } = this._config\n\n if (!this._element.ownerDocument.documentElement.contains(this.tip)) {\n container.append(tip)\n EventHandler.trigger(this._element, this.constructor.eventName(EVENT_INSERTED))\n }\n\n this._popper = this._createPopper(tip)\n\n tip.classList.add(CLASS_NAME_SHOW)\n\n // If this is a touch-enabled device we add extra\n // empty mouseover listeners to the body's immediate children;\n // only needed because of broken event delegation on iOS\n // https://www.quirksmode.org/blog/archives/2014/02/mouse_event_bub.html\n if ('ontouchstart' in document.documentElement) {\n for (const element of [].concat(...document.body.children)) {\n EventHandler.on(element, 'mouseover', noop)\n }\n }\n\n const complete = () => {\n EventHandler.trigger(this._element, this.constructor.eventName(EVENT_SHOWN))\n\n if (this._isHovered === false) {\n this._leave()\n }\n\n this._isHovered = false\n }\n\n this._queueCallback(complete, this.tip, this._isAnimated())\n }\n\n hide() {\n if (!this._isShown()) {\n return\n }\n\n const hideEvent = EventHandler.trigger(this._element, this.constructor.eventName(EVENT_HIDE))\n if (hideEvent.defaultPrevented) {\n return\n }\n\n const tip = this._getTipElement()\n tip.classList.remove(CLASS_NAME_SHOW)\n\n // If this is a touch-enabled device we remove the extra\n // empty mouseover listeners we added for iOS support\n if ('ontouchstart' in document.documentElement) {\n for (const element of [].concat(...document.body.children)) {\n EventHandler.off(element, 'mouseover', noop)\n }\n }\n\n this._activeTrigger[TRIGGER_CLICK] = false\n this._activeTrigger[TRIGGER_FOCUS] = false\n this._activeTrigger[TRIGGER_HOVER] = false\n this._isHovered = null // it is a trick to support manual triggering\n\n const complete = () => {\n if (this._isWithActiveTrigger()) {\n return\n }\n\n if (!this._isHovered) {\n this._disposePopper()\n }\n\n this._element.removeAttribute('aria-describedby')\n EventHandler.trigger(this._element, this.constructor.eventName(EVENT_HIDDEN))\n }\n\n this._queueCallback(complete, this.tip, this._isAnimated())\n }\n\n update() {\n if (this._popper) {\n this._popper.update()\n }\n }\n\n // Protected\n _isWithContent() {\n return Boolean(this._getTitle())\n }\n\n _getTipElement() {\n if (!this.tip) {\n this.tip = this._createTipElement(this._newContent || this._getContentForTemplate())\n }\n\n return this.tip\n }\n\n _createTipElement(content) {\n const tip = this._getTemplateFactory(content).toHtml()\n\n // TODO: remove this check in v6\n if (!tip) {\n return null\n }\n\n tip.classList.remove(CLASS_NAME_FADE, CLASS_NAME_SHOW)\n // TODO: v6 the following can be achieved with CSS only\n tip.classList.add(`bs-${this.constructor.NAME}-auto`)\n\n const tipId = getUID(this.constructor.NAME).toString()\n\n tip.setAttribute('id', tipId)\n\n if (this._isAnimated()) {\n tip.classList.add(CLASS_NAME_FADE)\n }\n\n return tip\n }\n\n setContent(content) {\n this._newContent = content\n if (this._isShown()) {\n this._disposePopper()\n this.show()\n }\n }\n\n _getTemplateFactory(content) {\n if (this._templateFactory) {\n this._templateFactory.changeContent(content)\n } else {\n this._templateFactory = new TemplateFactory({\n ...this._config,\n // the `content` var has to be after `this._config`\n // to override config.content in case of popover\n content,\n extraClass: this._resolvePossibleFunction(this._config.customClass)\n })\n }\n\n return this._templateFactory\n }\n\n _getContentForTemplate() {\n return {\n [SELECTOR_TOOLTIP_INNER]: this._getTitle()\n }\n }\n\n _getTitle() {\n return this._resolvePossibleFunction(this._config.title) || this._element.getAttribute('data-bs-original-title')\n }\n\n // Private\n _initializeOnDelegatedTarget(event) {\n return this.constructor.getOrCreateInstance(event.delegateTarget, this._getDelegateConfig())\n }\n\n _isAnimated() {\n return this._config.animation || (this.tip && this.tip.classList.contains(CLASS_NAME_FADE))\n }\n\n _isShown() {\n return this.tip && this.tip.classList.contains(CLASS_NAME_SHOW)\n }\n\n _createPopper(tip) {\n const placement = execute(this._config.placement, [this, tip, this._element])\n const attachment = AttachmentMap[placement.toUpperCase()]\n return Popper.createPopper(this._element, tip, this._getPopperConfig(attachment))\n }\n\n _getOffset() {\n const { offset } = this._config\n\n if (typeof offset === 'string') {\n return offset.split(',').map(value => Number.parseInt(value, 10))\n }\n\n if (typeof offset === 'function') {\n return popperData => offset(popperData, this._element)\n }\n\n return offset\n }\n\n _resolvePossibleFunction(arg) {\n return execute(arg, [this._element])\n }\n\n _getPopperConfig(attachment) {\n const defaultBsPopperConfig = {\n placement: attachment,\n modifiers: [\n {\n name: 'flip',\n options: {\n fallbackPlacements: this._config.fallbackPlacements\n }\n },\n {\n name: 'offset',\n options: {\n offset: this._getOffset()\n }\n },\n {\n name: 'preventOverflow',\n options: {\n boundary: this._config.boundary\n }\n },\n {\n name: 'arrow',\n options: {\n element: `.${this.constructor.NAME}-arrow`\n }\n },\n {\n name: 'preSetPlacement',\n enabled: true,\n phase: 'beforeMain',\n fn: data => {\n // Pre-set Popper's placement attribute in order to read the arrow sizes properly.\n // Otherwise, Popper mixes up the width and height dimensions since the initial arrow style is for top placement\n this._getTipElement().setAttribute('data-popper-placement', data.state.placement)\n }\n }\n ]\n }\n\n return {\n ...defaultBsPopperConfig,\n ...execute(this._config.popperConfig, [defaultBsPopperConfig])\n }\n }\n\n _setListeners() {\n const triggers = this._config.trigger.split(' ')\n\n for (const trigger of triggers) {\n if (trigger === 'click') {\n EventHandler.on(this._element, this.constructor.eventName(EVENT_CLICK), this._config.selector, event => {\n const context = this._initializeOnDelegatedTarget(event)\n context.toggle()\n })\n } else if (trigger !== TRIGGER_MANUAL) {\n const eventIn = trigger === TRIGGER_HOVER ?\n this.constructor.eventName(EVENT_MOUSEENTER) :\n this.constructor.eventName(EVENT_FOCUSIN)\n const eventOut = trigger === TRIGGER_HOVER ?\n this.constructor.eventName(EVENT_MOUSELEAVE) :\n this.constructor.eventName(EVENT_FOCUSOUT)\n\n EventHandler.on(this._element, eventIn, this._config.selector, event => {\n const context = this._initializeOnDelegatedTarget(event)\n context._activeTrigger[event.type === 'focusin' ? TRIGGER_FOCUS : TRIGGER_HOVER] = true\n context._enter()\n })\n EventHandler.on(this._element, eventOut, this._config.selector, event => {\n const context = this._initializeOnDelegatedTarget(event)\n context._activeTrigger[event.type === 'focusout' ? TRIGGER_FOCUS : TRIGGER_HOVER] =\n context._element.contains(event.relatedTarget)\n\n context._leave()\n })\n }\n }\n\n this._hideModalHandler = () => {\n if (this._element) {\n this.hide()\n }\n }\n\n EventHandler.on(this._element.closest(SELECTOR_MODAL), EVENT_MODAL_HIDE, this._hideModalHandler)\n }\n\n _fixTitle() {\n const title = this._element.getAttribute('title')\n\n if (!title) {\n return\n }\n\n if (!this._element.getAttribute('aria-label') && !this._element.textContent.trim()) {\n this._element.setAttribute('aria-label', title)\n }\n\n this._element.setAttribute('data-bs-original-title', title) // DO NOT USE IT. Is only for backwards compatibility\n this._element.removeAttribute('title')\n }\n\n _enter() {\n if (this._isShown() || this._isHovered) {\n this._isHovered = true\n return\n }\n\n this._isHovered = true\n\n this._setTimeout(() => {\n if (this._isHovered) {\n this.show()\n }\n }, this._config.delay.show)\n }\n\n _leave() {\n if (this._isWithActiveTrigger()) {\n return\n }\n\n this._isHovered = false\n\n this._setTimeout(() => {\n if (!this._isHovered) {\n this.hide()\n }\n }, this._config.delay.hide)\n }\n\n _setTimeout(handler, timeout) {\n clearTimeout(this._timeout)\n this._timeout = setTimeout(handler, timeout)\n }\n\n _isWithActiveTrigger() {\n return Object.values(this._activeTrigger).includes(true)\n }\n\n _getConfig(config) {\n const dataAttributes = Manipulator.getDataAttributes(this._element)\n\n for (const dataAttribute of Object.keys(dataAttributes)) {\n if (DISALLOWED_ATTRIBUTES.has(dataAttribute)) {\n delete dataAttributes[dataAttribute]\n }\n }\n\n config = {\n ...dataAttributes,\n ...(typeof config === 'object' && config ? config : {})\n }\n config = this._mergeConfigObj(config)\n config = this._configAfterMerge(config)\n this._typeCheckConfig(config)\n return config\n }\n\n _configAfterMerge(config) {\n config.container = config.container === false ? document.body : getElement(config.container)\n\n if (typeof config.delay === 'number') {\n config.delay = {\n show: config.delay,\n hide: config.delay\n }\n }\n\n if (typeof config.title === 'number') {\n config.title = config.title.toString()\n }\n\n if (typeof config.content === 'number') {\n config.content = config.content.toString()\n }\n\n return config\n }\n\n _getDelegateConfig() {\n const config = {}\n\n for (const [key, value] of Object.entries(this._config)) {\n if (this.constructor.Default[key] !== value) {\n config[key] = value\n }\n }\n\n config.selector = false\n config.trigger = 'manual'\n\n // In the future can be replaced with:\n // const keysWithDifferentValues = Object.entries(this._config).filter(entry => this.constructor.Default[entry[0]] !== this._config[entry[0]])\n // `Object.fromEntries(keysWithDifferentValues)`\n return config\n }\n\n _disposePopper() {\n if (this._popper) {\n this._popper.destroy()\n this._popper = null\n }\n\n if (this.tip) {\n this.tip.remove()\n this.tip = null\n }\n }\n\n // Static\n static jQueryInterface(config) {\n return this.each(function () {\n const data = Tooltip.getOrCreateInstance(this, config)\n\n if (typeof config !== 'string') {\n return\n }\n\n if (typeof data[config] === 'undefined') {\n throw new TypeError(`No method named \"${config}\"`)\n }\n\n data[config]()\n })\n }\n}\n\n/**\n * jQuery\n */\n\ndefineJQueryPlugin(Tooltip)\n\nexport default Tooltip\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap popover.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport Tooltip from './tooltip.js'\nimport { defineJQueryPlugin } from './util/index.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'popover'\n\nconst SELECTOR_TITLE = '.popover-header'\nconst SELECTOR_CONTENT = '.popover-body'\n\nconst Default = {\n ...Tooltip.Default,\n content: '',\n offset: [0, 8],\n placement: 'right',\n template: '' +\n '' +\n '' +\n '' +\n '
',\n trigger: 'click'\n}\n\nconst DefaultType = {\n ...Tooltip.DefaultType,\n content: '(null|string|element|function)'\n}\n\n/**\n * Class definition\n */\n\nclass Popover extends Tooltip {\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Overrides\n _isWithContent() {\n return this._getTitle() || this._getContent()\n }\n\n // Private\n _getContentForTemplate() {\n return {\n [SELECTOR_TITLE]: this._getTitle(),\n [SELECTOR_CONTENT]: this._getContent()\n }\n }\n\n _getContent() {\n return this._resolvePossibleFunction(this._config.content)\n }\n\n // Static\n static jQueryInterface(config) {\n return this.each(function () {\n const data = Popover.getOrCreateInstance(this, config)\n\n if (typeof config !== 'string') {\n return\n }\n\n if (typeof data[config] === 'undefined') {\n throw new TypeError(`No method named \"${config}\"`)\n }\n\n data[config]()\n })\n }\n}\n\n/**\n * jQuery\n */\n\ndefineJQueryPlugin(Popover)\n\nexport default Popover\n","/**\n * --------------------------------------------------------------------------\n * Bootstrap scrollspy.js\n * Licensed under MIT (https://github.com/twbs/bootstrap/blob/main/LICENSE)\n * --------------------------------------------------------------------------\n */\n\nimport BaseComponent from './base-component.js'\nimport EventHandler from './dom/event-handler.js'\nimport SelectorEngine from './dom/selector-engine.js'\nimport { defineJQueryPlugin, getElement, isDisabled, isVisible } from './util/index.js'\n\n/**\n * Constants\n */\n\nconst NAME = 'scrollspy'\nconst DATA_KEY = 'bs.scrollspy'\nconst EVENT_KEY = `.${DATA_KEY}`\nconst DATA_API_KEY = '.data-api'\n\nconst EVENT_ACTIVATE = `activate${EVENT_KEY}`\nconst EVENT_CLICK = `click${EVENT_KEY}`\nconst EVENT_LOAD_DATA_API = `load${EVENT_KEY}${DATA_API_KEY}`\n\nconst CLASS_NAME_DROPDOWN_ITEM = 'dropdown-item'\nconst CLASS_NAME_ACTIVE = 'active'\n\nconst SELECTOR_DATA_SPY = '[data-bs-spy=\"scroll\"]'\nconst SELECTOR_TARGET_LINKS = '[href]'\nconst SELECTOR_NAV_LIST_GROUP = '.nav, .list-group'\nconst SELECTOR_NAV_LINKS = '.nav-link'\nconst SELECTOR_NAV_ITEMS = '.nav-item'\nconst SELECTOR_LIST_ITEMS = '.list-group-item'\nconst SELECTOR_LINK_ITEMS = `${SELECTOR_NAV_LINKS}, ${SELECTOR_NAV_ITEMS} > ${SELECTOR_NAV_LINKS}, ${SELECTOR_LIST_ITEMS}`\nconst SELECTOR_DROPDOWN = '.dropdown'\nconst SELECTOR_DROPDOWN_TOGGLE = '.dropdown-toggle'\n\nconst Default = {\n offset: null, // TODO: v6 @deprecated, keep it for backwards compatibility reasons\n rootMargin: '0px 0px -25%',\n smoothScroll: false,\n target: null,\n threshold: [0.1, 0.5, 1]\n}\n\nconst DefaultType = {\n offset: '(number|null)', // TODO v6 @deprecated, keep it for backwards compatibility reasons\n rootMargin: 'string',\n smoothScroll: 'boolean',\n target: 'element',\n threshold: 'array'\n}\n\n/**\n * Class definition\n */\n\nclass ScrollSpy extends BaseComponent {\n constructor(element, config) {\n super(element, config)\n\n // this._element is the observablesContainer and config.target the menu links wrapper\n this._targetLinks = new Map()\n this._observableSections = new Map()\n this._rootElement = getComputedStyle(this._element).overflowY === 'visible' ? null : this._element\n this._activeTarget = null\n this._observer = null\n this._previousScrollData = {\n visibleEntryTop: 0,\n parentScrollTop: 0\n }\n this.refresh() // initialize\n }\n\n // Getters\n static get Default() {\n return Default\n }\n\n static get DefaultType() {\n return DefaultType\n }\n\n static get NAME() {\n return NAME\n }\n\n // Public\n refresh() {\n this._initializeTargetsAndObservables()\n this._maybeEnableSmoothScroll()\n\n if (this._observer) {\n this._observer.disconnect()\n } else {\n this._observer = this._getNewObserver()\n }\n\n for (const section of this._observableSections.values()) {\n this._observer.observe(section)\n }\n }\n\n dispose() {\n this._observer.disconnect()\n super.dispose()\n }\n\n // Private\n _configAfterMerge(config) {\n // TODO: on v6 target should be given explicitly & remove the {target: 'ss-target'} case\n config.target = getElement(config.target) || document.body\n\n // TODO: v6 Only for backwards compatibility reasons. Use rootMargin only\n config.rootMargin = config.offset ? `${config.offset}px 0px -30%` : config.rootMargin\n\n if (typeof config.threshold === 'string') {\n config.threshold = config.threshold.split(',').map(value => Number.parseFloat(value))\n }\n\n return config\n }\n\n _maybeEnableSmoothScroll() {\n if (!this._config.smoothScroll) {\n return\n }\n\n // unregister any previous listeners\n EventHandler.off(this._config.target, EVENT_CLICK)\n\n EventHandler.on(this._config.target, EVENT_CLICK, SELECTOR_TARGET_LINKS, event => {\n const observableSection = this._observableSections.get(event.target.hash)\n if (observableSection) {\n event.preventDefault()\n const root = this._rootElement || window\n const height = observableSection.offsetTop - this._element.offsetTop\n if (root.scrollTo) {\n root.scrollTo({ top: height, behavior: 'smooth' })\n return\n }\n\n // Chrome 60 doesn't support `scrollTo`\n root.scrollTop = height\n }\n })\n }\n\n _getNewObserver() {\n const options = {\n root: this._rootElement,\n threshold: this._config.threshold,\n rootMargin: this._config.rootMargin\n }\n\n return new IntersectionObserver(entries => this._observerCallback(entries), options)\n }\n\n // The logic of selection\n _observerCallback(entries) {\n const targetElement = entry => this._targetLinks.get(`#${entry.target.id}`)\n const activate = entry => {\n this._previousScrollData.visibleEntryTop = entry.target.offsetTop\n this._process(targetElement(entry))\n }\n\n const parentScrollTop = (this._rootElement || document.documentElement).scrollTop\n const userScrollsDown = parentScrollTop >= this._previousScrollData.parentScrollTop\n this._previousScrollData.parentScrollTop = parentScrollTop\n\n for (const entry of entries) {\n if (!entry.isIntersecting) {\n this._activeTarget = null\n this._clearActiveClass(targetElement(entry))\n\n continue\n }\n\n const entryIsLowerThanPrevious = entry.target.offsetTop >= this._previousScrollData.visibleEntryTop\n // if we are scrolling down, pick the bigger offsetTop\n if (userScrollsDown && entryIsLowerThanPrevious) {\n activate(entry)\n // if parent isn't scrolled, let's keep the first visible item, breaking the iteration\n if (!parentScrollTop) {\n return\n }\n\n continue\n }\n\n // if we are scrolling up, pick the smallest offsetTop\n if (!userScrollsDown && !entryIsLowerThanPrevious) {\n activate(entry)\n }\n }\n }\n\n _initializeTargetsAndObservables() {\n this._targetLinks = new Map()\n this._observableSections = new Map()\n\n const targetLinks = SelectorEngine.find(SELECTOR_TARGET_LINKS, this._config.target)\n\n for (const anchor of targetLinks) {\n // ensure that the anchor has an id and is not disabled\n if (!anchor.hash || isDisabled(anchor)) {\n continue\n }\n\n const observableSection = SelectorEngine.findOne(decodeURI(anchor.hash), this._element)\n\n // ensure that the observableSection exists & is visible\n if (isVisible(observableSection)) {\n this._targetLinks.set(decodeURI(anchor.hash), anchor)\n this._observableSections.set(anchor.hash, observableSection)\n }\n }\n }\n\n _process(target) {\n if (this._activeTarget === target) {\n return\n }\n\n this._clearActiveClass(this._config.target)\n this._activeTarget = target\n target.classList.add(CLASS_NAME_ACTIVE)\n this._activateParents(target)\n\n EventHandler.trigger(this._element, EVENT_ACTIVATE, { relatedTarget: target })\n }\n\n _activateParents(target) {\n // Activate dropdown parents\n if (target.classList.contains(CLASS_NAME_DROPDOWN_ITEM)) {\n SelectorEngine.findOne(SELECTOR_DROPDOWN_TOGGLE, target.closest(SELECTOR_DROPDOWN))\n .classList.add(CLASS_NAME_ACTIVE)\n return\n }\n\n for (const listGroup of SelectorEngine.parents(target, SELECTOR_NAV_LIST_GROUP)) {\n // Set triggered links parents as active\n // With both - and