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TY - JOUR AU - Hampe, Jochen AU - Franke, Andre AU - Rosenstiel, Philip AU - Till, Andreas AU - Teuber, Markus AU - Huse, Klaus AU - Albrecht, Mario AU - Mayr, Gabriele AU - De La Vega, Francisco M AU - Briggs, Jason AU - Günther, Simone AU - Prescott, Natalie J AU - Onnie, Clive M AU - Häsler, Robert AU - Sipos, Bence AU - Fölsch, Ulrich R AU - Lengauer, Thomas AU - Platzer, Matthias AU - Mathew, Christopher G AU - Krawczak, Michael AU - Schreiber, Stefan PY - 2007 DA - 2007/02/01 TI - A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 JO - Nature Genetics SP - 207 EP - 211 VL - 39 IS - 2 AB - 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. SN - 1546-1718 UR - https://doi.org/10.1038/ng1954 DO - 10.1038/ng1954 ID - Hampe2007 ER -