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A systematic evaluation of the performance and properties of the UK Biobank Polygenic Risk Score (PRS) Release.

Deborah J ThompsonDaniel WellsSaskia SelzamIliana PenevaRachel MooreKevin SharpWilliam A TarranEdward J BeardFernando Riveros-MckayCarla Giner-DelgadoDuncan PalmerPriyanka SethJames HarrisonMarta Futemanull nullGil McVeanVincent PlagnolPeter DonnellyMichael E Weale
Published in: PloS one (2024)
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.
Keyphrases
  • genome wide
  • machine learning
  • high resolution
  • dna methylation
  • systematic review
  • randomized controlled trial
  • gene expression
  • quality improvement
  • climate change
  • clinical evaluation
  • data analysis