Three open questions in polygenic score portability.

ABSTRACT: The broad adoption of polygenic scores (PGS) is hindered by their limited portability to people that differ-in genetic ancestry or other characteristics-from the GWAS samples used to construct them. Here, we measure PGS prediction accuracy as a continuous function of individuals' genome-wide genetic dissimilarity to the GWAS sample (genetic distance). Our results highlight three gaps in our understanding of PGS portability. First, variation in individual-level prediction accuracy is only weakly predicted by genetic distance. In fact, it is explained comparably well by socioeconomic measures. Second, trends of portability vary across traits. For several immunity-related traits, prediction accuracy drops near zero even at intermediate genetic distances-potentially reflecting fast evolutionar

SUBMITTER: Wang JY 

PROVIDER: S-EPMC12835231 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature