Polygenic Risk Scores Near Clinical Use but Equity and Standardisation Lag Behind
Polygenic risk scores can augment disease risk stratification by combining genetic predisposition with traditional risk factors, with promising applications in diagnostics, treatment selection, and clinical trial design. However, poor cross-ancestry transferability, lack of standardised scoring methods, and limited FAIR data sharing remain major barriers. Sustained community efforts are needed to ensure equitable and reproducible implementation.
The original study
Recent advances in polygenic scores: translation, equitability, methods and FAIR tools.
- Authors
- Xiang R, Kelemen M, Xu Y, Harris LW, Parkinson H, Inouye M, et al.
- Journal
- Genome medicine
- Type
- Journal Article, Review, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- PMID
- 38373998
Original abstract
Polygenic scores (PGS) can be used for risk stratification by quantifying individuals' genetic predisposition to disease, and many potentially clinically useful applications have been proposed. Here, we review the latest potential benefits of PGS in the clinic and challenges to implementation. PGS could augment risk stratification through combined use with traditional risk factors (demographics, disease-specific risk factors, family history, etc.), to support diagnostic pathways, to predict groups with therapeutic benefits, and to increase the efficiency of clinical trials. However, there exist challenges to maximizing the clinical utility of PGS, including FAIR (Findable, Accessible, Interoperable, and Reusable) use and standardized sharing of the genomic data needed to develop and recalculate PGS, the equitable performance of PGS across populations and ancestries, the generation of robust and reproducible PGS calculations, and the responsible communication and interpretation of results. We outline how these challenges may be overcome analytically and with more diverse data as well as highlight sustained community efforts to achieve equitable, impactful, and responsible use of PGS in healthcare.