Regenie WDL Workflow

This WDL workflow runs regenie for GWAS/RVAS. This has been tested on the UKB RAP, but not elsewhere.

This WDL parallelizes step 1 using the instructions here. It calls regenie v4.1 via a docker container provided by the RGC developers.

Available Workflows

• regenie_qt.WDL: Workflow for quantitative traits
• regenie_bt.WDL: Workflow for binary traits

Both workflows share the same structure and inputs, using a manifest file for step 2 chunks and plink2 filtering.

Workflow Inputs

Both workflows (regenie_qt.WDL and regenie_bt.WDL) share the same input parameters:

• File step1_pvar: The pvar file for step 1. Presumably, based on array genotypes have been filtered for MAF, HWE, missingness and LD pruned.
• File step1_psam: The psam file for step 1.
• File step1_pgen: The pgen file for step 1.
• String step1_prefix: The prefix for step 1 output files.
• File step2_chunk_manifest: The manifest file for step 2. This is a TSV listing chromosome regions and their corresponding pvar, psam, and pgen files. See below for details.
• String covariate_string: A string of covariate column names.
• String categorical_covariate_string: A string of categorical covariate column names.
• File plink2_binary: The plink2 binary file (zip archive). This is used to filter variants in step2 for improved performance.
• File covariates: The covariates file.
• File phenotypes: The phenotypes file.
• Boolean concatenate_into_parquet: Whether to concatenate the summary statistics into a single parquet file.
• Int n_step1: The number of "l0" jobs in step 1 to parallelize over.
• Boolean fix_step2_header_for_rap: The plink2 psam files from UKB RAP may have formatting issues. Setting this to true applies a workaround to fix the header.
• Int minMAC: The minimum minor allele count for variants in step 2 (default: 10).
• Int threads: Number of threads to use for computation (default: 8).
• Int step1_block_size: Block size for step 1 (default: 500).
• Int step2_block_size: Block size for step 2 (default: 250).

Step2 chunk manifest

> glimpse(manifest)
Rows: 316
Columns: 10
$ chrom                  <chr> "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1", "chr1"…
$ start                  <dbl> 1, 10000001, 20000001, 30000001, 40000001, 50000001, 60000001, 70000001, 80000001, 90000001, 100000001, 110000001, 120000001, 13000000…
$ end                    <dbl> 10000000, 20000000, 30000000, 40000000, 50000000, 60000000, 70000000, 80000000, 90000000, 100000000, 110000000, 120000000, 130000000, …
$ range                  <glue> "1:1-10000000", "1:10000001-20000000", "1:20000001-30000000", "1:30000001-40000000", "1:40000001-50000000", "1:50000001-60000000", "1…
$ plink2_chrom_pvar_name <glue> "/Bulk/DRAGEN WGS/DRAGEN population level WGS variants, PLINK format [500k release]/ukb24308_c1_b0_v1.pvar", "/Bulk/DRAGEN WGS/DRAGEN…
$ plink2_chrom_psam_name <glue> "/Bulk/DRAGEN WGS/DRAGEN population level WGS variants, PLINK format [500k release]/ukb24308_c1_b0_v1.psam", "/Bulk/DRAGEN WGS/DRAGEN…
$ plink2_chrom_pgen_name <glue> "/Bulk/DRAGEN WGS/DRAGEN population level WGS variants, PLINK format [500k release]/ukb24308_c1_b0_v1.pgen", "/Bulk/DRAGEN WGS/DRAGEN…
$ plink2_chrom_pvar      <chr> "file-Gjx9g7jJ8yxYff6BB47xf8f1", "file-Gjx9g7jJ8yxYff6BB47xf8f1", "file-Gjx9g7jJ8yxYff6BB47xf8f1", "file-Gjx9g7jJ8yxYff6BB47xf8f1", "f…
$ plink2_chrom_psam      <chr> "file-GzbyjvQJBx1VF1BGV57PGy64", "file-GzbyjvQJBx1VF1BGV57PGy64", "file-GzbyjvQJBx1VF1BGV57PGy64", "file-GzbyjvQJBx1VF1BGV57PGy64", "f…
$ plink2_chrom_pgen      <chr> "file-Gjx8kF0J8yxpF75qxKgg261X", "file-Gjx8kF0J8yxpF75qxKgg261X", "file-Gjx8kF0J8yxpF75qxKgg261X", "file-Gjx8kF0J8yxpF75qxKgg261X", "f…

Workflow Outputs

• File loco_list: The list of LOCO predictions from step 1.
• Array[File] locos: The array of LOCO files from step 1.
• Array[Array[File]] summary_stats: The summary statistics files from step 2.
• File parquet: The concatenated files from step2 into a single parquet file.

Dependencies

This project uses uv for python dependencies (e.g,. dxpy), though this not essential.

Contact

Contact Josh Weinstock for details on the WDL. Note, this repo has no affiliation with the REGENIE developers; please contact them for questions about REGENIE itself.

If you use this, please credit the regenie developers.