Genetics

This blog post reviews the ADAMS multi-ancestry genetic study of multiple sclerosis in the UK, which integrates GWAS, HLA allele imputation, and polygenic risk scoring in participants of South Asian and African genetic ancestry. It explains how the strongest susceptibility signals in both ancestries concentrate in the MHC—near HLA-DRB1 in South Asian participants and nearer HLA-A in African participants—while also evaluating the extent to which established European MS risk variants replicate across ancestries. The post summarizes the study’s evidence for shared but non-identical genetic architecture, highlights ancestry-dependent population-attributable burden for key alleles such as HLA-DRB115:01, and discusses why European-derived polygenic scores show attenuated performance outside Europe, motivating larger, better-powered multi-ancestry cohorts for equitable risk prediction and improved biological fine-mapping.