Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci

Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14747-52. doi: 10.1073/pnas.0706645104. Epub 2007 Sep 5.


Genome-wide association (GWA) studies offer a powerful unbiased method for the identification of multiple susceptibility genes for complex diseases. Here we report the results of a GWA study for Crohn's disease (CD) using family trios from the Quebec Founder Population (QFP). Haplotype-based association analyses identified multiple regions associated with the disease that met the criteria for genome-wide significance, with many containing a gene whose function appears relevant to CD. A proportion of these were replicated in two independent German Caucasian samples, including the established CD loci NOD2 and IBD5. The recently described IL23R locus was also identified and replicated. For this region, multiple individuals with all major haplotypes in the QFP were sequenced and extensive fine mapping performed to identify risk and protective alleles. Several additional loci, including a region on 3p21 containing several plausible candidate genes, a region near JAKMIP1 on 4p16.1, and two larger regions on chromosome 17 were replicated. Together with previously published loci, the spectrum of CD genes identified to date involves biochemical networks that affect epithelial defense mechanisms, innate and adaptive immune response, and the repair or remodeling of tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chromosomes, Human, Pair 17
  • Chromosomes, Human, Pair 3
  • Chromosomes, Human, Pair 4
  • Crohn Disease / genetics*
  • Crohn Disease / pathology
  • Founder Effect*
  • France / ethnology
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genetics, Population
  • Genome, Human*
  • Haplotypes
  • Humans
  • Nod2 Signaling Adaptor Protein / genetics
  • Physical Chromosome Mapping
  • Quebec
  • Receptors, Interleukin / genetics
  • Reproducibility of Results
  • Risk Factors


  • Genetic Markers
  • IL23R protein, human
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Receptors, Interleukin