Genetic risk variants in African Americans with multiple sclerosis

Noriko Isobe, Pierre Antoine Gourraud, Hanne F. Harbo, Stacy J. Caillier, Adam Santaniello, Pouya Khankhanian, Martin Maiers, Stephen Spellman, Nezih Cereb, Sooyoung Yang, Marcelo J. Pando, Laura Piccio, Anne H. Cross, Philip L. De Jager, Bruce A.C. Cree, Stephen L. Hauser, Jorge R. Oksenberg

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Objectives: To assess the association of established multiple sclerosis (MS) risk variants in 3,254 African Americans (1,162 cases and 2,092 controls). Methods: Human leukocyte antigen (HLA)-DRB1, HLA-DQB1, and HLA-A alleles were typed by molecular techniques. Single nucleotide polymorphism (SNP) genotyping was conducted for 76 MS-associated SNPs and 52 ancestry informative marker SNPs selected throughout the genome. Self-declared ancestry was refined by principal component analysis of the ancestry informative marker SNPs. An ancestry-adjusted multivariate model was applied to assess genetic associations. Results: The following major histocompatibility complex risk alleles were replicated: HLADRB1 15:01 (odds ratio [OR] 5 2.02 [95% confidence interval: 1.54-2.63], p 5 2.50e-07), HLA-DRB1 03:01 (OR 5 1.58 [1.29-1.94], p 5 1.11e-05), as well as HLA-DRB1 04:05 (OR 5 2.35 [1.26-4.37], p 5 0.007) and the African-specific risk allele of HLA-DRB1 15:03 (OR 5 1.26 [1.05-1.51], p 5 0.012). The protective association of HLA-A02:01 was confirmed (OR 5 0.72 [0.55-0.93], p 5 0.013). None of the HLA-DQB1 alleles were associated with MS. Using a significance threshold of p , 0.01, outside the major histocompatibility complex region, 8MS SNPs were also found to be associated with MS in African Americans. Conclusion: MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations.

Original languageEnglish
Pages (from-to)219-227
Number of pages9
JournalNeurology
Volume81
Issue number3
DOIs
StatePublished - Jul 16 2013

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