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          Institute: MPI für Informatik     Collection: Computational Biology and Applied Algorithmics     Display Documents

ID: 356622.0, MPI für Informatik / Computational Biology and Applied Algorithmics
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; Schreiber, Stefan
Date of Publication (YYYY-MM-DD):2007
Title of Journal:Nature Genetics
Issue / Number:2
Start Page:207
End Page:211
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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
Last Change of the Resource (YYYY-MM-DD):2008-03-10
External Publication Status:published
Document Type:Article
Communicated by:Thomas Lengauer
Affiliations:MPI für Informatik/Computational Biology and Applied Algorithmics
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