biostudies-literatureUnknown5(2)Breedon JRPolygenic risk scores aggregate an individual's burden of risk alleles to estimate the overall genetic risk for a specific trait or disease. Polygenic risk scores derived from genome-wide association studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk scores in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at multiple sclerosis prediction in a South Asian-ancestry population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-present), a study of ∼50 000 British-Bangladeshi and British-Pakistani individuals, and UKBrain communicationsfcad041https://www.ebi.ac.uk/biostudies/studies/S-EPMC10053643biostudies-literaturePolygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.PMC10053643Giovannoni GChaudhary SMcDermott JAnwar MMiah SCurtis CJDurham CMalawsky DMartin HGenes & Health Research TeamAkhtar SHussain SWinckley CLavery CWright JMacArthur DTrembath RCEto FBreen GMazid MBHarvey JColligan GHurles MRahman Svan Heel DAIslam KSafa NLerner RDurrani FHuang QQMcSweeney SHunt KAQureshi AMason DTahmasebi FMarshall CRChowdhury MArciero EDeloukas PBreedon JRNewman BSolly JFiner SHeng TOwor ETricker KUddin NMunir SChung RLee SHKhan ADobson RGarcia AAGriffiths CJacobs BMAshraf SAsgar OfalsePolygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.Polygenic risk scores aggregate an individual's burden of risk alleles to estimate the overall genetic risk for a specific trait or disease. Polygenic risk scores derived from genome-wide association studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk scores in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at multiple sclerosis prediction in a South Asian-ancestry population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-present), a study of ∼50 000 British-Bangladeshi and British-Pakistani individuals, and UK2023-01-01T00:00:00Z20232025-04-22T18:10:50.24Z2025-02-19T00:13:30.578ZS-EPMC100536433700633110.1093/braincomms/fcad041