Genetic risk variants in African Americans with multiple sclerosis

被引：47

作者：

Isobe, Noriko ^{[1
]}

Gourraud, Pierre-Antoine ^{[1
]}

Harbo, Hanne F. ^{[2
]}

Caillier, Stacy J. ^{[1
]}

Santaniello, Adam ^{[1
]}

Khankhanian, Pouya ^{[1
]}

Maiers, Martin ^{[3
]}

Spellman, Stephen ^{[4
]}

Cereb, Nezih ^{[5
]}

Yang, SooYoung ^{[5
]}

Pando, Marcelo J. ^{[6
]}

Piccio, Laura ^{[7
]}

Cross, Anne H. ^{[7
]}

De Jager, Philip L. ^{[8
,9
,10
,11
,12
]}

Cree, Bruce A. C. ^{[1
]}

Hauser, Stephen L. ^{[1
]}

Oksenberg, Jorge R. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA

[2] Oslo Univ Hosp, Dept Neurol, Oslo, Norway

[3] Natl Marrow Donor Program, Minneapolis, MN USA

[4] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA

[5] Histogenetics LLC, Ossining, NY USA

[6] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[7] Washington Univ, Dept Neurol, St Louis, MO USA

[8] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA

[9] Brigham & Womens Hosp, Dept Psychiat, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Boston, MA USA

[11] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA

[12] MIT, Cambridge, MA 02139 USA

来源：

NEUROLOGY | 2013年 / 81卷 / 03期

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; INFORMATIVE MARKERS; ALLELES; HLA; ADMIXTURE; METAANALYSIS; POPULATION; ANCESTRY; HLA-DRB1;

D O I：

10.1212/WNL.0b013e31829bfe2f

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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(star) 15:01 (odds ratio [OR] = 2.02 [95% confidence interval: 1.54-2.63], p = 2.50e-07), HLA-DRB1(star) 03: 01 (OR = 1.58 [1.29-1.94], p = 1.11e-05), as well as HLA-DRB1(star) 04:05 (OR = 2.35 [1.26-4.37], p = 0.007) and the African-specific risk allele of HLA-DRB1(star) 15:03 (OR = 1.26 [1.05-1.51], p = 0.012). The protective association of HLA-A(star) 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, 8MS 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.

引用

页码：219 / 227

页数：9

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