title: Genetic risk variants in African Americans with multiple sclerosis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  MS genetic risk in African Americans only partially overlaps with that of Europeans and could explain the difference of MS prevalence between populations.
authors.affiliation: Department of Neurology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Noriko
authors.initials: N
authors.lastname: Isobe
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Gourraud
authors.forename: Hanne F
authors.initials: HF
authors.lastname: Harbo
authors.forename: Stacy J
authors.initials: SJ
authors.lastname: Caillier
authors.forename: Adam
authors.initials: A
authors.lastname: Santaniello
authors.forename: Pouya
authors.initials: P
authors.lastname: Khankhanian
authors.forename: Martin
authors.initials: M
authors.lastname: Maiers
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Nezih
authors.initials: N
authors.lastname: Cereb
authors.forename: SooYoung
authors.initials: S
authors.lastname: Yang
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Pando
authors.forename: Laura
authors.initials: L
authors.lastname: Piccio
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D015234:HLA-A Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains