Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3

Nat Genet. 2014 Sep;46(9):1007-11. doi: 10.1038/ng.3061. Epub 2014 Aug 10.

Abstract

To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, P(combined) = 3.42 × 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, P(combined) = 2.97 × 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, P(combined) = 1.26 × 10(-118), OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics
  • Case-Control Studies
  • Chromosomes, Human, Pair 1*
  • Chromosomes, Human, Pair 10*
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Promoter Regions, Genetic
  • Uveomeningoencephalitic Syndrome / genetics*