Genetic risk variants in African Americans with multiple sclerosis.

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 < 0.01, outside the major histocompatibility complex region, 8 MS 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.

journal_name

Neurology

journal_title

Neurology

authors

Isobe N,Gourraud PA,Harbo HF,Caillier SJ,Santaniello A,Khankhanian P,Maiers M,Spellman S,Cereb N,Yang S,Pando MJ,Piccio L,Cross AH,De Jager PL,Cree BA,Hauser SL,Oksenberg JR

doi

10.1212/WNL.0b013e31829bfe2f

subject

Has Abstract

pub_date

2013-07-16 00:00:00

pages

219-27

issue

3

eissn

0028-3878

issn

1526-632X

pii

WNL.0b013e31829bfe2f

journal_volume

81

pub_type

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