PRSbils

Updates

Introduction

Polygenic risk score with bilevel continuous shrinkage for incorporating functional annotations.

How to use

1. Download/Clone PRSbils (this repository) to your local machine
2. Install required python packages: pip3 install -r requirements.txt
3. Get the input files ready

• Download and extract LD reference panel from 1000 Genomes Project phase 3 (the same procedure as in PRSCS):
  • African
  • American
  • East Asian
  • European
  • South-eastern Asian
• Genotype file
• GWAS summary statistics
• Mapping file from SNPs to annotation groups

4. Run PRSbils.py to get the trained weights for SNPs with different functional annotations.

Sample command

You can test the program using the following bash command after downloading the 1000G European LD referenfce panel file under the home directory:

pip3 install -r requirements.txt

python3 PRSbils.py \
        --ref_dir=./1000G/ldblk_1kg_eur \
        --bim_prefix=./data/genotypes_plink_chr1_train \
        --sst_file=./data/sumstat.txt \
        --map_file=./data/snpmap.txt \
        --n_gwas=50000 \
        --out_dir=./data/output_trained_weights_prsbils \
        --chrom=1 \
        --n_iter=1000 \
        --thres=1e-04 \
        --beta_std=False \
        --flip=True

The output file is ./data/output_trained_weights_prsbils_beta_chr1.txt, which is a tab-delimited text file with the following columns:

[Chromosome] [SNP ID] [SNP Position] [Allele 1] [Allele 2] [Weight in the summary statistics file] [Weight from PRSbils] [Annotation Group] [Subgroup (not yet implemented)] [Allele Frequency]

Please check the next section or run python3 PRSbils.py --help for details about the parameters.

Details about the parameters

usage: PRSbils.py [-h] --ref_dir REF_DIR --bim_prefix BIM_PREFIX --sst_file
                  SST_FILE --map_file MAP_FILE [--map_gcol MAP_GCOL] --n_gwas
                  N_GWAS --out_dir OUT_DIR [--a A] [--b B] [--c C] [--d D]
                  [--e E] [--f F] [--n_iter N_ITER]
                  [--chrom CHROM [CHROM ...]] [--beta_std [BETA_STD]]
                  [--thres THRES] [--ignore_blk [IGNORE_BLK]]
                  [--verbose [VERBOSE]] [--fixtau [FIXTAU]] [--flip [FLIP]]

PRSbils: Polygenic Risk Score with Bilevel Continuous Shrinkage

optional arguments:
  -h, --help            show this help message and exit
  --ref_dir REF_DIR     Full path (including folder name) to the directory
                        (ldblk_1kg_eur, ldblk_1kg_eas or ldblk_1kg_afr) that
                        contains information on the LD reference panel
                        (snpinfo_1kg_hm3 and ldblk_1kg_chr*.hdf5)
  --bim_prefix BIM_PREFIX
                        Full path and the prefix of the bim file
  --sst_file SST_FILE   Full path and the file name of the GWAS summary
                        statistics Summary statistics file must be tab
                        delimited with the following format (including the
                        header line): SNP A1 A2 BETA P Or: SNP A1 A2 OR P
  --map_file MAP_FILE   Full path and the file name of the mapping file from
                        SNPs to sets. Map file must have the MSigDB file
                        format : [CHROM] [SNPID] [SETNAME] [GROUP (optional)]
  --map_gcol MAP_GCOL   (Not yet implemented) Column id for group info in map_file. Default is None
                        (no group information)
  --n_gwas N_GWAS       Sample size of the GWAS
  --out_dir OUT_DIR     Output directory and output filename prefix of the
                        posterior effect size estimates
  --a A                 Parameter a for sigma. Default is 0.001
  --b B                 Parameter b in the gamma prior for sigma. Default is
                        0.001
  --c C                 Parameter c for group implementation. Default is 0.001
  --d D                 Parameter d for group implementation. Default is 0.001
  --e E                 Parameter e for lambda. Default is 1
  --f F                 Parameter f for lambda. Default is 0.5
  --n_iter N_ITER       Number of maximum iterations. Default is 1000
  --chrom CHROM [CHROM ...]
                        The chromosome on which the model is fitted. Default
                        is iterating through 22 autosomes
  --beta_std [BETA_STD]
                        Boolean. If True, return standardized posterior SNP
                        effect sizes. Default is False
  --thres THRES         Threshold value for convergence. Default is 0.001
  --ignore_blk [IGNORE_BLK]
                        Boolean. If false, elements categorized as same set
                        but in different ld will be treated as different sets.
                        Default is False
  --verbose [VERBOSE]   Boolean. Default is False
  --fixtau [FIXTAU]     Boolean. If false, will estimate tau in algorithm,
                        otherwise will fix at 1. Default is False
  --flip [FLIP]         Boolean. If false, signs of beta in summary statistics
                        will not be flipped when there's a switch in A1 and A2
                        alleles. Default is False