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UK Biobank release and systematic evaluation of optimised polygenic risk scores for 53 diseases and quantitative traits
Open accessAbstract
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.
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“The PRS was derived using external Genome-wide association study (GWAS) training data and has been validated for its association with Late-Onset Alzheimer’s Disease (LOAD) within the UKB.80”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [80]
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The UK Biobank resource with deep phenotyping and genomic data
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Proteomic signatures improve risk prediction for common and rare diseases
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“Participants provided written informed consent.”
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“We compared the performance of MILTON models trained on 67 quantitative traits (Methods) with those trained on the respective disease-specific PRS 13 of a given phenotype, or all 36 standard PRSs available in the UKB.”
Influential
Metadata
- Authors
- Thompson, D. J., Wells, D., Selzam, S., Peneva, I., Moore, R., Sharp, K., Tarran, W. A., Beard, E. J., Riveros-Mckay, F., Giner-Delgado, C., Palmer, D., Seth, P., Harrison, J., Futema, M., Genomics England Research Consortium, McVean, G., Plagnol, V., Donnelly, P., & Weale, M. E.
- Affiliations
- Genomics (United Kingdom) (GB)
- St George's, University of London (GB)
- Corresponding author
- Weale, Michael E.
- ORCID
- Venue
- medRxiv
- Publisher
- openRxiv
- Published
- 2022-06-16
- OpenAlex
- W4283067507
- Cited by
- 280
- References
- 41
- Citations by year
- 2026: 47 · 2025: 84 · 2024: 109 · 2023: 32 · 2022: 8
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by
- Locations
- medRxiv (acceptedVersion, cc-by)
- Funders
- Medical Research Council (MC_PC_17228)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- polygenic risk score, UK Biobank, disease risk prediction, quantitative traits, genetic risk prediction, clinical utility
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