Susceptibility loci reported in genome-wide association studies are associated with Crohn's disease in Canadian children

Aliment Pharmacol Ther. 2010 Jun;31(11):1186-91. doi: 10.1111/j.1365-2036.2010.04294.x. Epub 2010 Mar 8.


Background: Recent genome-wide association studies based on adult and paediatric populations have implicated >30 genes/loci as susceptibility loci for Crohn's disease (CD).

Aims: To investigate whether reported genes/loci were also associated with CD in Canadian children.

Design and methods: A case-control design was implemented at three paediatric gastroenterology clinics in Canada. Children < or =18 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in five genome-wide association studies reported genes/loci were genotyped. Associations between individual SNPs and CD were examined.

Results: A total of 406 cases and 415 controls were studied. The mean (+/-s.d.) age of the cases was 12.3 (+/-3.2) years. Most cases were male (56.6%), had ileo-colonic disease (L3 +/- L4, 52.0%) and inflammatory behaviour (B1 +/- p, 86.9%) at diagnosis. Allelic association analysis (two-tailed) showed that three of the five targeted SNPs were significantly associated with overall susceptibility for CD (ZNF365, r10995271, P = 0.001; PTPN2, rs1893217, P = 0.005; STAT3, rs744166, P = 0.01). Associations with SNP rs4613763 in the PTGER4 locus were marginally nonsignificant (P = 0.07). The ZNF365 and STAT3 SNPs were predominantly associated with ileal disease with or without colonic involvement.

Conclusion: The identified susceptibility genes/loci for adult-onset CD also confer risk for paediatric-onset CD.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Canada / epidemiology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Crohn Disease / epidemiology
  • Crohn Disease / genetics*
  • Female
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease* / epidemiology
  • Genome
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Risk Factors