Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency

Nat Genet. 2010 Sep;42(9):777-80. doi: 10.1038/ng.644. Epub 2010 Aug 8.


To understand the genetic predisposition to selective immunoglobulin A deficiency (IgAD), we performed a genome-wide association study in 430 affected individuals (cases) from Sweden and Iceland and 1,090 ethnically matched controls, and we performed replication studies in two independent European cohorts. In addition to the known association of HLA with IgAD, we identified association with a nonsynonymous variant in IFIH1 (rs1990760G>A, P = 7.3 x 10(-10)) which was previously associated with type 1 diabetes and systemic lupus erythematosus. Variants in CLEC16A, another known autoimmunity locus, showed suggestive evidence for association (rs6498142C>G, P = 1.8 x 10(-7)), and 29 additional loci were identified with P < 5 x 10(-5). A survey in IgAD of 118 validated non-HLA autoimmunity loci indicated a significant enrichment for association with autoimmunity loci as compared to non-autoimmunity loci (P = 9.0 x 10(-4)) or random SNPs across the genome (P < 0.0001). These findings support the hypothesis that autoimmune mechanisms may contribute to the pathogenesis of IgAD.

Publication types

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

MeSH terms

  • Alleles
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / genetics
  • Autoimmunity / genetics*
  • Case-Control Studies
  • DEAD-box RNA Helicases / genetics*
  • Finland
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Iceland
  • IgA Deficiency / etiology
  • IgA Deficiency / genetics*
  • IgA Deficiency / immunology
  • Interferon-Induced Helicase, IFIH1
  • Risk
  • Spain
  • Sweden
  • Validation Studies as Topic


  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1