Association between genome-wide association studies reported SNPs and pediatric-onset Crohn’s disease in Canadian children
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A recent pediatric-focused genome-wide association study has implicated three novel susceptibility loci for Crohn’ disease (CD).We aimed to investigate whether the three recently reported and other previously reported genes/loci were also associated with CD in Canadian children. A case–control design was implemented at three pediatric gastroenterology clinics in Canada. Children <19 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in 19 reported genes/loci were genotyped. Associations between individual SNPs and CD were examined. A total of 563 cases and 553 controls were studied. The mean (±SD) age of the cases was 12.3 (±3.2) years. Most cases were male (56.0%), had ileo-colonic disease (L3 ± L4, 48.8%) and inflammatory behavior (B1 ± p, 87.9%) at diagnosis. Allelic association analysis (two-tailed) showed that 8 of the 19 targeted SNPs were significantly associated with overall susceptibility for CD. Associations with one additional SNP was borderline non-significant. Significantly associated SNPs included SNPs rs1250550 (p = 0.026) and rs8049439 (p = 0.04), recently reported to be specifically associated with pediatric-onset CD.Based on the results, we confirmed associations between two of the three novel pediatric-CD loci and other regions reported for associations with either pediatric and/or adult-onset CD.
We would like to thank Drs. Willis B. and Jarvis J. and Mack A. for facilitating the recruitment of orthopedic controls at the Ottawa (CHEO) study site. The study was funded by the Canadian Institutes of Health Research (CIHR-IBD NET GRANT, Institute of Infection & Immunity). Dr. Amre is supported by a research salary award from the Fonds de la Recherché en Santé du Québec (FRSQ). Dr. Seidman is supported by a Research Chair Award from the Crohn’s and Colitis Foundation of Canada (CCFC) and the CIHR.
- Amre DK, Mack DR, Morgan K et al (2010) Susceptibility loci reported in genome-wide association studies are associated with Crohn’s disease in children. Aliment Pharmacol Therap (Epub ahead of print)Google Scholar