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

P>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 < 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.