Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population

• DOI: 10.1371/journal.pone.0279132
• Publication Date: 2022-12-22T18:34:58Z
• Authors: Ashley H. Beecham; Lilyana Amezcua; Angel Chinea; Clara P. Manrique; Lissette Gomez; Andrea Martinez; Gary W. Beecham; Nikolaos A. Patso...; Tanuja Chitnis; Howard L. Weiner; Philip L. De Jager; Esteban G. Burchard; Brett T. Lund; Kathryn C. Fitzge...; Peter A. Calabresi; Silvia R. Delgado; Jorge R. Oksenberg; Jacob L. McCauley
• Keywords: Linkage Disequilibrium; Genetic predisposition

The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across region explaining 20% of heritability in European populations. Variation is high populations allele frequency differences and population-specific risk alleles identified. We sought identify MHC-specific MS susceptibility variants assess effect ancestral modification within 2652 Latinx Hispanic individuals as well 2435 Black African American individuals. have identified several novel which are rare including HLA-B*53:01, we utilized differing linkage disequilibrium patterns inherent these an role for HLA-DRB1*15:01 HLA-DQB1*06:02 on risk. found a decrease Native ancestry cases vs controls MHC, peaking near previously MICB locus ~5.5% Hispanics ~0.4% Americans. variants, gene region, show global indicate may be due part correlated environmental factors. also modified by local true differences; carriers almost two times carriers. These results validate importance investigating at level offer insight into epidemiology phenotypic diversity.