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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.
GLOSSARY
- AIM=
- ancestry informative marker;
- CI=
- confidence interval;
- GWAS=
- genome-wide association studies;
- HLA=
- human leukocyte antigen;
- LD=
- linkage disequilibrium;
- MAF=
- minor allele frequencies;
- MHC=
- major histocompatibility complex;
- MS=
- multiple sclerosis;
- OR=
- odds ratio;
- PC=
- principal component;
- SNP=
- single nucleotide polymorphism
Footnotes
The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, or any other agency of the US government.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received November 30, 2012.
- Accepted in final form April 4, 2013.
- © 2013 American Academy of Neurology
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