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P367. Analysis of 33 Crohn's disease risk loci in Chinese inflammatory bowel disease patients shows role of autophagy in CD individuals

C. Ooi1, K. Ling1, K. Thia1, M. Seielstad2

1Singapore General Hospital, Singapore, Singapore; 2Genome Institute of Singapore, Singapore, Singapore

Introduction: GWAS studies resulted in identification of numerous loci confirming the IBD genetic risk. More than 30 confirmed loci are associated with Crohn's disease in Caucasians. Some of the CD loci have also been shown to influence UC risk.

Method: We examine evidence of association for 40 SNPs identified in a recent GWAS meta-analysis of populations of European origins [1]. We genotyped 42 CD patients (aged 18–65, 50.0% males), 74 UC patients (aged 16–70, 71.4% males) and 547 common controls (aged 24–80, 72.7% males). Single nucleotide polymorphisms (SNPs) at each CD-locus were selected based on previous associations and genotyped. Quality control filters were applied to SNPs and samples with call-rate less than 90%, minor allele frequency (<1%), and Hardy-Weinberg equilibrium in controls (P < 0.001) before the analysis. 33 SNPs were tested for association with CD and UC by trend tests implemented in PLINK.

Results: We replicated with nominal significance (P < 0.05) SNPs in or near STAT3, and the autophagy genes IRGM and ATG16L1 for association solely with CD. SNPs in NKX2–3 and ZNF365 are the only CD derived loci nominally associated (P < 0.05) with UC in our cohort. It is worth mentioning that our most significant associations are near the NKX2–3 loci.

Conclusion: We are not able to find any shared associations for CD and UC in our Chinese patient sample. Nevertheless, the conspicuous signal near NKX2–3 may not be due to coincidence alone. In addition, we provide supportive data for a role of autophagy in CD pathophysiology in an Asian cohort.

1. JC Barrett, S Hansoul, DL Nicolae, et al. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease, Nature Genetics 2008, 40, 955–962.