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Increased risk of multiple sclerosis risk in African Americans due to genes – June 2013

Genetic risk variants in African Americans with multiple sclerosis

Neurology 10.1212/WNL.0b013e31829bfe2f
Noriko Isobe, MD, PhD,
Pierre-Antoine Gourraud, PhD, MPH,
Hanne F. Harbo, MD, PhD,
Stacy J. Caillier, BS,
Adam Santaniello, BS,
Pouya Khankhanian, BA,
Martin Maiers, MS,
Stephen Spellman, MBS,
Nezih Cereb, MD,
SooYoung Yang, PhD,
Marcelo J. Pando, PhD,
Laura Piccio, MD, PhD,
Anne H. Cross, MD,
Philip L. De Jager, MD, PhD,
Bruce A.C. Cree, MD, PhD, MCR,
Stephen L. Hauser, MD and
Jorge R. Oksenberg, PhD Jorge.Oksenberg at ucsf.edu

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.
Received November 30, 2012, Accepted in final form April 4, 2013.

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