Genetics

This blog post examines Rivier et al. (2025), which evaluates how a multiple sclerosis (MS) genetic risk score (GRS) constructed from 232 established MS-associated variants performs across ancestry groups in the U.S. “All of Us” Research Program. Using matched samples of European, African, and Latino/admixed participants (32,428 per group) and electronic health record–based MS phenotyping, the study shows robust risk stratification in European and Latino/admixed cohorts but limited discriminatory power in African-ancestry participants—highlighting a core limitation of polygenic score portability when discovery GWAS are Eurocentric. The post then discusses how applying JointPRS substantially improves stratification in the African-ancestry cohort, underscoring that performance gaps are not inevitable but can be reduced through multi-ancestry methodology and better representation in genetic discovery efforts, with direct implications for equitable translation of polygenic risk tools in MS.