|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Isobe, 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 Published||2013 Jul 16|
|Keywords||Adult, 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.
|PubMed Central ID||PMC3770164|
|Grant List||HHSH234200637020C / / 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