Background

A new feature of PRSice is the ability to perform set base/pathway based analysis. This new feature is called PRSet.

Paper on PRSet currently under preparation.

Preparation

PRSet is based on PRSice, with additional input requirements

Input

• PRSice.R file: A wrapper for the PRSice binary and for plotting
• PRSice binary file: Perform all analysis except plotting
• Base data set: GWAS summary results, which the PRS is based on
• Target data set: Raw genotype data of "target phenotype". Can be in the form of PLINK binary or BGEN

PRSet Specific Input

• Bed file(s): Bed file(s) containing region of genes within a gene set; or
• MSigDB file: File containing name of each gene sets and the ID of genes within the gene set on each individual line. If MSigDB is provided, GTF file is required.
• GTF file: A file contain the genome boundary of each individual gene
• SNP file: A file containing SNPs constituting the gene set of interest. Can be in MSigDB (gmt) format or a file contain a single column of SNP IDs.

Running PRSet

In most case, assuming the PRSice binary is located in ($HOME)/PRSice/bin/ and the working directory is ($HOME)/PRSice, you can run PRSet with the following commands:

With MSigDB data

Assuming a MSigDB file (set.txt) is downloaded and a gene gtf file (gene.gtf) from Ensemble is available, PRSet can then be performed using:

Rscript PRSice.R \
    --prsice ./bin/PRSice \
    --base TOY_BASE_GWAS.assoc \
    --target TOY_TARGET_DATA \
    --binary-target T \
    --thread 1 \
    --gtf gene.gtf \
    --msigdb set.txt \
    --multi-plot 10

This will perform PRSet analysis and generate the multi-set plot with the top 10 gene sets

With Bed Files

Alternatively, if a list of bed files are available, e.g. A.bed,B.bed, PRSet can be performed by running

Rscript PRSice.R \
    --prsice ./bin/PRSice \
    --base TOY_BASE_GWAS.assoc \
    --target TOY_TARGET_DATA \
    --binary-target T \
    --thread 1 \
    --bed A.bed:SetA,B.bed \
    --multi-plot 10

With SNP Set

Finally, if you want to construct sets based on a list of SNPs, you can use --snp-set:

Rscript PRSice.R \
    --prsice ./bin/PRSice \
    --base TOY_BASE_GWAS.assoc \
    --target TOY_TARGET_DATA \
    --binary-target T \
    --thread 1 \
    --snp-set A.snp:A,B.snp \
    --multi-plot 10

Two different format are allowed:

• SNP Set list format: A file containing a single column of SNP ID. Name of the set will be the file name or can be provided using --snp-set File:Name
• MSigDB format: Each row represent a single SNP set with the first column containing the name of the SNP set.