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Neurology DOI:10.1212/WNL.0b013e31829bfe2f

Genetic risk variants in African Americans with multiple sclerosis.

Publication TypeJournal Article
Year of Publication2013
AuthorsIsobe, N, Gourraud, P-A, Harbo, HF, Caillier, SJ, Santaniello, A, Khankhanian, P, Maiers, M, Spellman, S, Cereb, N, Yang, SY, Pando, MJ, Piccio, L, Cross, AH, De Jager, PL, Cree, BAC, Hauser, SL, Oksenberg, JR
Date Published2013 Jul 16
KeywordsAdult, African Americans, Age of Onset, Alleles, Case-Control Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, HLA-A Antigens, HLA-DQ beta-Chains, HLA-DRB1 Chains, Humans, Male, Middle Aged, Multiple Sclerosis, Polymorphism, Single Nucleotide

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: HLA-DRB1*15:01 (odds ratio [OR] = 2.02 [95% confidence interval: 1.54-2.63], p = 2.50e-07), HLA-DRB1*03:01 (OR = 1.58 [1.29-1.94], p = 1.11e-05), as well as HLA-DRB1*04:05 (OR = 2.35 [1.26-4.37], p = 0.007) and the African-specific risk allele of HLA-DRB1*15:03 (OR = 1.26 [1.05-1.51], p = 0.012). The protective association of HLA-A*02:01 was confirmed (OR = 0.72 [0.55-0.93], p = 0.013). None of the HLA-DQB1 alleles were associated with MS. Using a significance threshold of p

CONCLUSION: MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations.


Alternate JournalNeurology
PubMed ID23771490
PubMed Central IDPMC3770164
Grant ListHHSH234200637020C / / PHS HHS / United States
R01NS046297 / NS / NINDS NIH HHS / United States
R01NS076492 / NS / NINDS NIH HHS / United States
RC2 GM093080 / GM / NIGMS NIH HHS / United States