Genetic risk variants in African Americans with multiple sclerosis.

Neurology
Authors
Keywords
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: 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.

Year of Publication
2013
Journal
Neurology
Volume
81
Issue
3
Pages
219-27
Date Published
2013 Jul 16
ISSN
1526-632X
URL
DOI
10.1212/WNL.0b013e31829bfe2f
PubMed ID
23771490
PubMed Central ID
PMC3770164
Links
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