Concepedia

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

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,

medRxiv · 2022 · 268 citations · 26 references

DOI Full text

Open access

Concepts

Life SciencesGeneticsHealth InformaticsGenomic Data AnalysisMedical GeneticsPrecision MedicineDisease PhenotypingGenetic Risk PredictionGenomic PredictionPolygenic Risk AssessmentQuantitative Trait AnalysisRisk StratificationGenomic Prediction In Human Disease RiskGenomic Risk PredictionPolygenic Risk Score ConstructionPolygenic Risk ScoringPolygenic Risk StratificationRisk Prediction For Complex TraitsSoftware Benchmarking

TL;DR

The study introduces the UK Biobank Polygenic Risk Score Release, providing PRSs for 28 diseases and 25 quantitative traits, and a benchmarking tool for comparing PRSs within the same cohort. The release includes validated PRS algorithms, benchmarked against 81 published scores, and the software enables like‑for‑like performance evaluation across diseases and traits, with additional validation in external cohorts. Benchmarking demonstrates that the UKB PRSs outperform most published scores, and the comprehensive set of 53 traits on a common cohort enhances evidence for their clinical utility.

Abstract

Abstract 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.