Genetics

This blog post critically examines a genomics study evaluating whether a multiple sclerosis (MS) polygenic risk score (PRS), derived from 282 established MS-associated variants, generalizes across diverse genetic ancestry groups within the All of Us Research Program. It outlines the study design, PRS construction, and EHR-based MS phenotyping, then synthesizes the main finding: robust risk stratification in participants of European and Latino/admixed American ancestry, but substantially weaker and statistically non-significant performance in African ancestry participants after adjustment for covariates. The post interprets these results through established principles of PRS portability—linkage disequilibrium differences, allele frequency variation, and potential effect-size heterogeneity—and concludes with implications for equitable precision medicine, emphasizing the necessity of larger, ancestrally diverse MS GWAS and ancestry-aware PRS development.