A systematic evaluation of the performance and properties of the UK Biobank Polygenic Risk Score (PRS) Release
Deborah J. Thompson, Daniel Wells, Saskia Selzam, Iliana Peneva, Rachel Moore, Kevin Sharp, William A. Tarran, Edward J. Beard, Fernando Riveros-Mckay, Carla Giner-Delgado, Duncan S. Palmer, Priyanka Seth, Jamie Harrison, Marta Futema, Gil McVean, Vincent Plagnol, Peter Donnelly, Michael E. Weale
Abstract
We assess the UK Biobank (UKB) Polygenic Risk Score (PRS) Release, a set of PRSs for 28 diseases and 25 quantitative traits that has been made available on the individuals in UKB, using a unified pipeline for PRS evaluation. We also release a benchmarking software tool to enable like-for-like performance evaluation for different PRSs for the same disease or trait. Extensive benchmarking shows the PRSs in the UKB Release to outperform a broad set of 76 published PRSs. For many of the diseases and traits we also validate the PRS algorithms in a separate cohort (100,000 Genomes Project). The availability of PRSs for 53 traits on the same set of individuals also allows a systematic assessment of their properties, and the increased power of these PRSs increases the evidence for their potential clinical benefit.