Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians

Genes Immun. 2008 Oct;9(7):624-30. doi: 10.1038/gene.2008.59. Epub 2008 Jul 24.

Abstract

A recent genome-wide association study (GWAS) conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC) identified a number of putative MS susceptibility genes. Here we have performed a replication study in 1134 Australian MS cases and 1265 controls for 17 risk-associated single nucleotide polymorphisms (SNPs) reported by the IMSGC. Of 16 SNPs that passed quality control filters, four, each corresponding to a different non-human leukocyte antigen (HLA) gene, were associated with disease susceptibility: KIAA0350 (rs6498169) P=0.001, IL2RA (rs2104286) P=0.033, RPL5 (rs6604026) P=0.041 and CD58 (rs12044852) P=0.042. There was no association (P=0.58) between rs6897932 in the IL7R gene and the risk of MS. No interactions were detected between the replicated IMSGC SNPs and HLA-DRB1*15, gender, disease course, disease progression or age-at-onset. We used a novel Bayesian approach to estimate the extent to which our data increased or decreased evidence for association with the six most-associated IMSGC loci. These analyses indicated that even modest P-values, such as those reported here, can contribute markedly to the posterior probability of 'true' association in replication studies. In conclusion, these data provide support for the involvement of four non-HLA genes in the pathogenesis of MS, and combined with previous data, increase to genome-wide significance (P=3 x 10(-8)) evidence of an association between KIAA0350 and risk of disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Australia
  • CD58 Antigens / genetics*
  • Case-Control Studies
  • Child
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Interleukin-2 Receptor alpha Subunit / genetics*
  • Lectins, C-Type / genetics*
  • Male
  • Middle Aged
  • Monosaccharide Transport Proteins / genetics*
  • Multiple Sclerosis / genetics*
  • Polymorphism, Single Nucleotide
  • Ribosomal Proteins / genetics*

Substances

  • CD58 Antigens
  • CLEC16A protein, human
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Monosaccharide Transport Proteins
  • Ribosomal Proteins
  • ribosomal protein L5