The GenoPred Pipeline: A Comprehensive and Scalable Pipeline for Polygenic Scoring

Abstract

Abstract Motivation Polygenic scoring is an approach for estimating an individual’s likelihood of a given outcome. Polygenic scores are typically calculated from genome-wide association study (GWAS) summary statistics and individual-level genotype data for the target sample. Going from genotype to interpretable polygenic scores involves many steps and there are many methods available, limiting the accessibility of polygenic scores for research and clinical application. Additional challenges exist for studies in ancestrally diverse populations. We have implemented the leading polygenic scoring methodologies within an easy-to-use pipeline called GenoPred. Results Here we present the GenoPred pipeline, an easy-to-use, high-performance, reference-standardised and reproducible workflow for polygenic scoring. It requires minimal inputs and offers various configuration options to cater to a range of use-cases. GenoPred implements a comprehensive set of analyses, including genotype and GWAS quality control, target sample ancestry inference, polygenic score file generation using a range of leading methods, and target sample scoring. GenoPred standardises the polygenic scoring process using reference genetic data, providing interpretable polygenic scores. The pipeline is applicable to GWAS and target data from any population within the reference, facilitating studies of diverse ancestry. GenoPred is a Snakemake pipeline with associated Conda software environments, ensuring reproducibility. We apply the pipeline to UK Biobank data demonstrating the pipeline’s simplicity, efficiency, and performance. The GenoPred pipeline provides a novel resource for polygenic scoring, integrating a range of complex processes within an easy-to-use framework. GenoPred widens access of the leading polygenic scoring methodology and their application to studies of diverse ancestry. Availability and Implementation Freely available on the web at https://github.com/opain/GenoPred. Supplementary information Supplementary information are available at Bioinformatics online. Further information is also provided on the GenoPred pipeline website: Https://opain.github.io/GenoPred/pipeline_overview.html