Multiple Common Variants for Celiac Disease Influencing Immune Gene Expression

Nat Genet. 2010 Apr;42(4):295-302. doi: 10.1038/ng.543. Epub 2010 Feb 28.

Abstract

We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression.

Publication types

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

MeSH terms

  • Case-Control Studies
  • Celiac Disease / genetics*
  • Gene Expression
  • Gene Expression Profiling
  • Genes, MHC Class I*
  • Genome-Wide Association Study
  • Humans
  • Meta-Analysis as Topic
  • Polymorphism, Single Nucleotide*
  • Risk

Associated data

  • GEO/GSE20142
  • GEO/GSE20332