Genome-wide association study of ulcerative colitis identifies three new susceptibility loci including the HNF4A region

摘要

Ulcerative colitis (UC) is a common form of inflammatory bowel disease with a complex aetiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for UC in 2361 cases and 5417 controls. Loci showing evidence of association at P < 1 × 10⁻⁵ were followed up by genotyping in an independent set of 2321 cases and 4818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 × 10⁻¹⁷), 16q22 (CDH1 and CDH3; P = 2.8 × 10⁻⁸) and 7q31 (LAMB1; 3.0 × 10⁻⁸). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, which is an established complication of longstanding UC. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of UC.