PGS Calculator

Applying polygenic scores (PGS) on imputed genotypes

Features

• command line program (works on linux or MacOS)
• supports vcf.gz files (imputed or genotyped)
• supports different filters (e.g. r2 or variant list)
• supports PGS Catalog format (https://www.pgscatalog.org, currently over 2,000 scores)
• creates an interactive html report

Installation

• Download pgs-calc-*.tar.gz from latest release
• Extract the downloaded archive (e.g tar -xf bash installer.sh)
• Validate installation with ./pgs-calc --version

Usage

Applying polygenic scores (PGS) on imputed genotypes

./pgs-calc apply --ref PGS000018 --out PGS000018.scores.txt chr*.dose.noID.vcf.gz  --report-html PGS000018.html

All scores are written to file PGS000018.scores.txt and an interactive report html report is created.

Optional parameters

• --minR2 <value> - Use only variants with an imputation quality (R2) >= <value>:
• --writeVariants <file> - Writes csv file with all variants used in calculation
• --includeVariants <file> - Restrict calculation to use only variants from this csv file
• --genotypes GT|DS - Use genotypes or dosage
• --report-html <file> - Creates an interactive html report. The report includes summary statistics (like coverage) for each score and can be filtered by e.g. id or trait.

Input files

Genotypes

• VCF file format (*.vcf and *.vcf.gz)
• one VCF file per chromosome (e.g. output of Imputationserver)
• works out of the box with imputed genotypes from Michigan Imputation Server

Scores

./pgs-calc supports PGSCatalog out of the box: open the website, find your score of interest and download the provided txt.gz files.

Examples

Single chromosome

Apply PGS to a single file (e.g. one chromosome):

./pgs-calc apply --ref PGS000018.txt.gz test.chr1.vcf.gz --out scores.txt

All scores are written to file scores.txt

Multiple chromosomes

Apply PGS to multiple files (e.g. multiple chromosomes):

./pgs-calc apply --ref PGS000018.txt.gz test.chr1.vcf.gz test.chr2.vcf.gz test.chr3.vcf.gz test.chr4.vcf.gz --out scores.txt

Apply PGS to multiple files by using file patterns:

./pgs-calc apply --ref PGS000018.txt.gz test.chr*.vcf.gz --out scores.txt

Multiple scores

Apply multiple score files:

./pgs-calc apply --ref PGS000018.txt.gz,PGS000027.txt.gz test.chr*.vcf.gz --out scores.txt

Filter by Imputation Qualitity

Use only variants with an imputation quality (R2) >= 0.9:

./pgs-calc apply --ref PGS000018.txt.gz test.chr*.vcf.gz --minR2 0.9 --out scores.txt

PGSCatalog support

If a PGS id is provided, pgs-calc downloads the file from PGSCatalog automatically:

./pgs-calc apply --ref PGS000018 test.chr1.vcf.gz --out scores.txt

All scores are written to file scores.txt

Contact

Lukas Forer, Institute of Genetic Epidemiology, Medical University of Innsbruck