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- Title
A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1.
- Authors
Hampe, Jochen; Franke, Andre; Rosenstiel, Philip; Till, Andreas; Teuber, Markus; Huse, Klaus; Albrecht, Mario; Mayr, Gabriele; De La Vega, Francisco M.; Briggs, Jason; Günther, Simone; Prescott, Natalie J.; Onnie, Clive M.; Häsler, Robert; Sipos, Bence; Fölsch, Ulrich R.; Lengauer, Thomas; Platzer, Matthias; Mathew, Christopher G.; Krawczak, Michael
- Abstract
We performed a genome-wide association study of 19,779 nonsynonymous SNPs in 735 individuals with Crohn disease and 368 controls. A total of 7,159 of these SNPs were informative. We followed up on all 72 SNPs with P ≤ 0.01 with an allele-based disease association test in 380 independent Crohn disease trios, 498 Crohn disease singleton cases and 1,032 controls. Disease association of rs2241880 in the autophagy-related 16-like 1 gene (ATG16L1) was replicated in these samples (P = 4.0 × 10−8) and confirmed in a UK case-control sample (P = 0.0004). By haplotype and regression analysis, we found that marker rs2241880, a coding SNP (T300A), carries virtually all the disease risk exerted by the ATG16L1 locus. The ATG16L1 gene encodes a protein in the autophagosome pathway that processes intracellular bacteria. We found a statistically significant interaction with respect to Crohn disease risk between rs2241880 and the established CARD15 susceptibility variants (P = 0.039). Together with the lack of association between rs2241880 and ulcerative colitis (P > 0.4), these data suggest that the underlying biological process may be specific to Crohn disease.
- Subjects
CROHN'S disease; INFLAMMATORY bowel diseases; ULCERATIVE colitis; PROKARYOTES; COLON diseases; BACTERIA
- Publication
Nature Genetics, 2007, Vol 39, Issue 2, p207
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng1954