GWAS-identified multiple sclerosis risk loci involved in immune response: validation in Russians

J Neuroimmunol. 2015 May 15:282:85-91. doi: 10.1016/j.jneuroim.2015.03.015. Epub 2015 Mar 17.

Abstract

Multiple sclerosis (MS) is a chronic neuro-inflammatory disease of complex etiology. The results of GWAS, a high-throughput method to discover genetic architecture of MS, require replication in independent ethnic groups. We performed a replication study of nine GWAS-identified SNPs in immune response in Russians. Associations of CLEC16A and IL2RA with MS were validated. Besides, we observed the associations of CLEC16A and IRF8 in women, and IL7RA and CD58 in men. With multi-locus association analysis two protective biallelic combinations: (TNFRSF1A*T+CLEC16A*A) and (TNFRSF1A*T+IRF8*A) were identified in women. Associations of CLEC16A*G/G and both biallelic combinations in women with MS survived the permutation test.

Keywords: GWAS validation; Multiple sclerosis; Risk allele; SNP; Susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Disability Evaluation
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Lectins, C-Type / genetics
  • Male
  • Middle Aged
  • Monosaccharide Transport Proteins / genetics
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology*
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Russia
  • Severity of Illness Index
  • Sex Factors
  • Young Adult

Substances

  • CLEC16A protein, human
  • IL2RA protein, human
  • Interferon Regulatory Factors
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Monosaccharide Transport Proteins
  • Receptors, Tumor Necrosis Factor, Type I
  • TNFRSF1A protein, human
  • interferon regulatory factor-8