Mapping Multiple Sclerosis Susceptibility to the HLA-DR Locus in African Americans

Jorge R. Oksenberg, Lisa F. Barcellos, Bruce A.C. Cree, Sergio E. Baranzini, Teodorica L. Bugawan, Omar Khan, Robin R. Lincoln, Amy Swerdlin, Emmanuel Mignot, Ling Lin, Douglas Goodin, Henry A. Erlich, Silke Schmidt, Glenys Thomson, David E. Reich, Margaret A. Pericak-Vance, Jonathan L. Haines, Stephen L. Hauser

Research output: Contribution to journalArticle

254 Scopus citations

Abstract

An underlying complex genetic susceptibility exists in multiple sclerosis (MS), and an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been repeatedly demonstrated in high-risk (northern European) populations. It is unknown whether the effect is explained by the HLA-DRB1 or the HLA-DQB1 gene within the susceptibility haplotype, which are in strong linkage disequilibrium (LD). African populations are characterized by greater haplotypic diversity and distinct patterns of LD compared with northern Europeans. To better localize the HLA gene responsible for MS susceptibility, case-control and family-based association studies were performed for DRB1 and DQB1 loci in a large and well-characterized African American data set. A selective association with HLA-DRB1*15 was revealed, indicating a primary role for the DRB1 locus in MS independent of DQB1*0602. This finding is unlikely to be solely explained by admixture, since a substantial proportion of the susceptibility chromosomes from African American patients with MS displayed haplotypes consistent with an African origin.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
JournalAmerican journal of human genetics
Volume74
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Oksenberg, J. R., Barcellos, L. F., Cree, B. A. C., Baranzini, S. E., Bugawan, T. L., Khan, O., Lincoln, R. R., Swerdlin, A., Mignot, E., Lin, L., Goodin, D., Erlich, H. A., Schmidt, S., Thomson, G., Reich, D. E., Pericak-Vance, M. A., Haines, J. L., & Hauser, S. L. (2004). Mapping Multiple Sclerosis Susceptibility to the HLA-DR Locus in African Americans. American journal of human genetics, 74(1), 160-167. https://doi.org/10.1086/380997