Polygenic Risk Score (PRS) Calculation

Prerequisite

• R

• R packages:

  # Install packages in R
  
  install.packages('BEDMatrix')
  install.packages('data.table')
  install.packages('parallel')

Test

• Clone the repository

git clone https://github.com/now2014/B2PRS.git

• Test in R

Here, the genotype data in the B2PRS/test-bed/ directory, which comes from the 1000 Genomes Project.

bed.file.pattern <- 'B2PRS/test-bed/1kg-eur-chr@.bed' # @ is replaced by chromosome number
source('B2PRS/B2PRS.r')

# max number of SNPs to be read from bed file in each chunk
# for bed file with large number of samples, reduce chunk.size to avoid memory overflow, e.g., 1e3
chunk.size <- 1e3 # test for small bed file with 5 samples


PRS.results <- PRS.wg(
  EAF.b.rds='B2PRS/PRS-b/MaleScore/EAF.b.SumHEM.FEMALE_n16600_xgb_pred_proba.regenie.rds',
  snp.info.rds='B2PRS/PRS-b/snp.info.SumHEM.LDpred.rds',
  bed.file.pattern=bed.file.pattern, fill.missing=c('mean'), chunk.size=chunk.size,
  mc.cores=1, PRS.name='PRS.SumHEM.FEMALE_n16600'
)

print(PRS.results)
###### Output for the test #######
#         PRS.SumHEM.FEMALE_n16600
# HG00096               0.02322992
# HG00097               0.01947996
# HG00099               0.02164128
# HG00101               0.02291205
# HG00102               0.02969029

Parameters of the PRS.wg function

Param	Default	Meaning
EAF.b.rds	'./PRS-b/EAF.b.rds'	path to the RDS file with 'EAF' and 'b' for PRS calculation
snp.info.rds	'./PRS-b/snp.info.rds'	path to the RDS file with SNP information
bed.file.pattern	'./chr@.bed'	a pattern of bed file names, where '@' is replaced by chromosome number
fill.missing	'mean'	a string of 'EAF' or 'mean' to fill missing genotype with 'EAF' column or 'mean' frequency derived from the input genotype data
chunk.size	1000	max number of SNPs to be read from bed file in each chunk
mc.cores	1	number of cores for parallel computing
PRS.name	'PRS'	name of the PRS column in the output

Input RDS files

• Please make sure that each row of the data.frame in the snp.info.rds matches the corresponding row of the data.frame in the EAF.b.rds.

• Columns in snp.info.rds

  head(readRDS('B2PRS/PRS-b/snp.info.SumHEM.LDpred.rds'))
  #   CHROM    POS       rsid EA OA
  # 1     1 752721  rs3131972  G  A
  # 2     1 754182  rs3131969  G  A
  # 3     1 760912  rs1048488  T  C
  # 4     1 768448 rs12562034  A  G
  # 5     1 779322  rs4040617  G  A
  # 6     1 838555  rs4970383  A  C

  CHROM (required): Chromosome number (1, 2, 3, ..., 22, 23)

  POS (optional): GRCh37 position

  rsid (required): RSID

  EA (required): Effect Allele

  OA (required): Other allele

• Columns in the EAF.b.rds

  head(readRDS('B2PRS/PRS-b/MaleScore/EAF.b.SumHEM.FEMALE_n16600_xgb_pred_proba.regenie.rds'))
  #        EAF             b
  # 1 0.838825  2.734815e-10
  # 2 0.868619  1.987269e-06
  # 3 0.838086 -4.706651e-10
  # 4 0.106446  1.674726e-06
  # 5 0.129488 -2.342625e-06
  # 6 0.244398 -7.139709e-06

  EAF (required): Effect Allele Frequency

  b (required): Independent genetic effect of EA

Pre-computed RDS files

This repository contains several pre-computed RDS files stored in the ./PRS-b directory:

1. TopSNPs method (LD pruned ($r^2$ < 0.1) variants with GWAS p-value < 5e-8)

• snp.info.rds

GWAS sumstats	snp.info.rds
MaleScore/ALL_n30677	MaleScore/snp.info.TopSNPs.ALL_n30677_xgb_pred_proba.regenie.rds
MaleScore/FEMALE_n16600	MaleScore/snp.info.TopSNPs.FEMALE_n16600_xgb_pred_proba.regenie.rds
MaleScore/MALE_n14077	MaleScore/snp.info.TopSNPs.MALE_n14077_xgb_pred_proba.regenie.rds
ProtSexGap/FEMALE_n16600	ProtSexGap/snp.info.TopSNPs.FEMALE_n16600_ProtSexGap.rds
ProtSexGap/MALE_n14077	ProtSexGap/snp.info.TopSNPs.MALE_n14077_ProtSexGap.rds

• EAF.b.rds

GWAS sumstats	EAF.b.rds
MaleScore/ALL_n30677	MaleScore/EAF.b.TopSNPs.ALL_n30677_xgb_pred_proba.regenie.rds
MaleScore/FEMALE_n16600	MaleScore/EAF.b.TopSNPs.FEMALE_n16600_xgb_pred_proba.regenie.rds
MaleScore/MALE_n14077	MaleScore/EAF.b.TopSNPs.MALE_n14077_xgb_pred_proba.regenie.rds
ProtSexGap/FEMALE_n16600	ProtSexGap/EAF.b.TopSNPs.FEMALE_n16600_ProtSexGap.rds
ProtSexGap/MALE_n14077	ProtSexGap/EAF.b.TopSNPs.MALE_n14077_ProtSexGap.rds

2. SumHEM method

• snp.info.rds='PRS-b/snp.info.SumHEM.LDpred.rds'
• EAF.b.rds

GWAS sumstats	EAF.b.rds
MaleScore/ALL_n30677	MaleScore/EAF.b.SumHEM.ALL_n30677_xgb_pred_proba.regenie.rds
MaleScore/FEMALE_n16600	MaleScore/EAF.b.SumHEM.FEMALE_n16600_xgb_pred_proba.regenie.rds
MaleScore/MALE_n14077	MaleScore/EAF.b.SumHEM.MALE_n14077_xgb_pred_proba.regenie.rds
ProtSexGap/META_n30677	ProtSexGap/EAF.b.SumHEM.META_n30677_ProtSexGap.rds
ProtSexGap/FEMALE_n16600	ProtSexGap/EAF.b.SumHEM.FEMALE_n16600_ProtSexGap.rds
ProtSexGap/MALE_n14077	ProtSexGap/EAF.b.SumHEM.MALE_n14077_ProtSexGap.rds

3. LDpred method

• snp.info.rds='PRS-b/snp.info.SumHEM.LDpred.rds'
• EAF.b.rds

Model	GWAS sumstats	EAF.b.rds
LDpred-auto	MaleScore/ALL_n30677	MaleScore/EAF.b.LDpred-Auto.ALL_n30677_xgb_pred_proba.regenie.rds
LDpred-auto	MaleScore/FEMALE_n16600	MaleScore/EAF.b.LDpred-Auto.FEMALE_n16600_xgb_pred_proba.regenie.rds
LDpred-auto	MaleScore/MALE_n14077	MaleScore/EAF.b.LDpred-Auto.MALE_n14077_xgb_pred_proba.regenie.rds
LDpred-inf	MaleScore/ALL_n30677	MaleScore/EAF.b.LDpred-Inf.ALL_n30677_xgb_pred_proba.regenie.rds
LDpred-inf	MaleScore/FEMALE_n16600	MaleScore/EAF.b.LDpred-Inf.FEMALE_n16600_xgb_pred_proba.regenie.rds
LDpred-inf	MaleScore/MALE_n14077	MaleScore/EAF.b.LDpred-Inf.MALE_n14077_xgb_pred_proba.regenie.rds
LDpred-auto	ProtSexGap/META_n30677	ProtSexGap/EAF.b.LDpred-Auto.META_n30677_ProtSexGap.rds
LDpred-auto	ProtSexGap/FEMALE_n16600	ProtSexGap/EAF.b.LDpred-Auto.FEMALE_n16600_ProtSexGap.rds
LDpred-auto	ProtSexGap/MALE_n14077	ProtSexGap/EAF.b.LDpred-Auto.MALE_n14077_ProtSexGap.rds
LDpred-inf	ProtSexGap/META_n30677	ProtSexGap/EAF.b.LDpred-Inf.META_n30677_ProtSexGap.rds
LDpred-inf	ProtSexGap/FEMALE_n16600	ProtSexGap/EAF.b.LDpred-Inf.FEMALE_n16600_ProtSexGap.rds
LDpred-inf	ProtSexGap/MALE_n14077	ProtSexGap/EAF.b.LDpred-Inf.MALE_n14077_ProtSexGap.rds