| Title: | Recommendations for responsible use of population descriptors in polygenic risk score development |
| Journal: | Nature Genetics |
| Published: | 24 Nov 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41286102/ |
| DOI: | https://doi.org/10.1038/s41588-025-02395-9 |
| URL: | https://pmc.ncbi.nlm.nih.gov/articles/PMC12817171/ |
Publication 18825
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Abstract
The recent report from the National Academies of Sciences, Engineering and Medicine emphasizes the importance of detailed and tailored use of population descriptors in genomic analyses, but specific guidance for genomic data analysts is still lacking. In this Perspective, we focus on polygenic risk score (PRS) development and demonstrate that population descriptors are explicitly or implicitly involved in every step of the process. Attention to this matter is both an analytical concern and an ethical concern, as each decision has an impact on PRS results and performance across diverse populations. Drawing from the experience of the Polygenic Risk Methods Development (PRIMED) Consortium, we offer recommendations for applying population descriptors throughout the entire process of PRS development, validation and application. We urge the research community, particularly data analysts, to critically evaluate and justify their choices when using these descriptors to ensure both scientific rigor and research integrity.</p>
8 Keywords
- Genetic Predisposition to Disease
- Genetic Risk Score
- Genome-Wide Association Study
- Genomics
- Humans
- Multifactorial Inheritance
- Risk Assessment
- Risk Factors
26 Authors
- Johanna L. Smith
- Clement A. Adebamowo
- Sally N. Adebamowo
- Burcu F. Darst
- Stephanie M. Fullerton
- Stephanie M. Gogarten
- Marwan E. Hamed
- Jibril B. Hirbo
- Micah R. Hysong
- Angad Singh Johar
- Alyna T. Khan
- Iftikhar J. Kullo
- Iain R. Konigsberg
- Peter Kraft
- Leslie A. Lange
- Yun Li
- Alicia R. Martin
- Sarah C. Nelson
- Ananyo Choudhury
- Michèle Ramsay
- Ewan K. Cobran
- Daniel J. Schaid
- Jayati Sharma
- Ying Wang
- Genevieve L. Wojcik
- Quan Sun
1 Application
| Application ID | Title |
|---|---|
| 25953 | Transcriptome-wide Association Study of Cardiometabolic Traits in the UK Biobank Cohort |
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