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Canadian Journal of Gastroenterology
Volume 24 (2010), Issue 5, Pages 297-302
Original Article

Replication and Meta-Analysis of 13,000 Cases Defines the Risk for Interleukin-23 Receptor and Autophagy-Related 16-Like 1 Variants in Crohn’s Disease

Lynn Cotterill,1 Debbie Payne,2 Scott Levison,3 John McLaughlin,3 Emma Wesley,4 Mark Feeney,4 Hilary Durbin,4 Simon Lal,5 Alistair Makin,6 Simon Campbell,6 Stephen A Roberts,7 Catherine O’Neill,3 Cathryn Edwards,4 and William G Newman1

1Department of Medical Genetics, Manchester Academic Health; Science Centre, St Mary’s Hospital and University of Manchester, United Kingdom
2Centre for Integrated Genomic Medical Research (CIGMR), University of Manchester, United Kingdom
3Department of Gastrointestinal Sciences, University of Manchester, Manchester, United Kingdom
4Gastroenterology Unit, Torbay Hospital, Torbay, United Kingdom
5Gastroenterology Unit, University Hospital Aintree, Liverpool, United Kingdom
6Department of Gastroenterology, Manchester Royal Infirmary, United Kingdom
7Health Research Methodology Group, University of Manchester, Manchester, United Kingdom

Received 8 May 2009; Accepted 22 July 2009

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


BACKGROUND/OBJECTIVE: Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn’s disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed.

METHODS: British Caucasian subjects with inflammatory bowel disease (n=500) and 877 ethnically matched controls were genotyped for the disease-associated variants in IL23R and ATG16L1. In addition, meta-analyses of 12,991 patients and 14,598 controls, and 11,909 patients and 15,798 controls, were conducted on independently published data for the associations between IL23R and ATG16L1 variants and CD, respectively.

RESULTS: In the present cohort, both susceptibility variants showed highly significant associations, including IL23R (rs11209026, P=0.0006; OR 0.37; 95% CI 0.21 to 0.67) and ATG16L1 (rs2241880, P=0.0017; OR 1.36; 95% CI 1.12 to 1.66). The meta-analysis based on the random effects model showed similar combined effects for rs11209026 (n=26, OR 0.41; 95% CI 0.37 to 0.46) and rs2241880 (n=25, OR 1.33; 95% CI 1.28 to 1.39). There was no statistically significant gene-gene interaction between caspase recruitment domain (CARD15) variants and the IL23R or ATG16L1 polymorphisms (P=0.44 and P=0.24, respectively).

CONCLUSION: The present cohort and meta-analysis provides strong evidence that, in addition to CARD15, polymorphisms in both IL23R and ATG16L1 alter susceptibility to CD and that these effects are consistent across all populations of European ancestry; however, only ATG16L1 is relevant to inflammatory bowel disease in the Asian population.