Polygenic indexes (PGIs) trained on samples of European genetic ancestries often lose substantial predictive power when applied to non-European ancestries. While this portability problem is well recog...

Human populations differ in disease prevalences and in average values of phenotypes, but the extent to which differences are caused by genetic or environmental factors is unknown for most complex trai...

Nature Reviews Genetics, Published online: 05 September 2025; doi:10.1038/s41576-025-00893-4The accuracy of polygenic scores (PGS) remains limited and poorly transferable across ancestries. In this Comment, Zeng and Visscher discuss how integrating functional annotations with whole-genome sequencing data can improve PGS by prioritizing likely causal variants shared across populations and by assigning greater weight to variants in biologically relevant regions.

Non-communicable diseases (NCDs) such as cardiovascular diseases, chronic respiratory diseases, cancers, diabetes, and mental health disorders pose a significant global health challenge, accounting fo...