UK Biobank release and systematic evaluation of optimised polygenic risk scores for 53 diseases and quantitative traits

We present and assess the UK Biobank (UKB) Polygenic Risk Score (PRS) Release, a set of PRSs for 28 diseases and 25 quantitative traits being made available on the individuals in UKB. 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 81 published PRSs. For many of the diseases and traits we also validate the PRS algorithms in other cohorts. 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. ### Competing Interest Statement Peter Donnelly and Gil McVean are partners in Peptide Groove LLP. All other authors declare no competing interests. ### Funding Statement This work was funded by Genomics plc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: UK Biobank data use (Project Application Number 9659) was approved by the UK Biobank according to their established access procedures, and legal and ethical approval is covered by the Research Tissue Bank approval obtained from the UK Biobank's governing Research Ethics Committee (REC 16/NW/0274), as recommended by the National Research Ethics Service. Our use of 100,000 Genomes Project data was approved by Genomics England's Access Review Committee under application reference AR88. Legal and ethical approval for our use of dbGaP cohort data is provided by the Western Institutional Review Board (Study Number 1264897, IRB Tracking Number 20192201). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The polygenic risk scores computed for each individual in UK Biobank have been made available to all approved UK Biobank researchers through the data showcase mechanism. The new GWAS data have been made available via .