Follow-up study of the first genome-wide association scan in alopecia areata: IL13 and KIAA0350 as susceptibility loci supported with genome-wide significance

J Invest Dermatol. 2012 Sep;132(9):2192-7. doi: 10.1038/jid.2012.129. Epub 2012 Apr 26.

Abstract

Recently, the first genome-wide association study (GWAS) of alopecia areata (AA) was conducted in a North-American sample, and this identified eight susceptibility loci surpassing genome-wide significance. The aim of the present follow-up association analysis was to confirm five of these eight loci (single-nucleotide polymorphisms (SNPs) from the CTLA4, IL-2RA, and HLA regions were not included due to previous own findings) and test 12 other loci from the GWAS, which did not surpass the threshold for genome-wide significance. Twenty-three SNPs from the 17 loci were investigated using a sample of 1,702 Central European AA patients and 1,723 controls. Of the five loci with previously reported genome-wide significance, association was confirmed for all of these: ULBP3/ULBP6, PRDX5, IL-2/IL-21, STX17, and IKZF4/ERBB3 (P-value <0.05). To detect robust evidence for association among the 12 other loci, a meta-analysis of the present association data and the data of the recent GWAS was performed. Genome-wide significant association was found for rs20541 (P(comb)=7.52 × 10(-10); odds ratio (OR)=1.30 (1.23-1.38)) and rs998592 (P(comb)=1.11 × 10(-11); OR=1.28 (1.21-1.36)), thus establishing IL-13 and KIAA0350/CLEC16A as susceptibility loci for AA. Interestingly, IL-13 and KIAA0350/CLEC16A are susceptibility loci for other autoimmune diseases, supporting the hypothesis of shared pathways of autoimmune susceptibility.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alopecia Areata / genetics*
  • Autoimmune Diseases / genetics
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Interleukin-13 / genetics*
  • Lectins, C-Type / genetics*
  • Middle Aged
  • Monosaccharide Transport Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Young Adult

Substances

  • CLEC16A protein, human
  • Interleukin-13
  • Lectins, C-Type
  • Monosaccharide Transport Proteins