TY - JOUR T1 - Association mapping of inflammatory bowel disease loci to single variant resolution JF - bioRxiv DO - 10.1101/028688 SP - 028688 AU - Hailiang Huang AU - Ming Fang AU - Luke Jostins AU - Maša Umićević Mirkov AU - Gabrielle Boucher AU - Carl A Anderson AU - Vibeke Andersen AU - Isabelle Cleynen AU - Adrian Cortes AU - François Crins AU - Mauro D’Amato AU - Valérie Deffontaine AU - Julia Dimitrieva AU - Elisa Docampo AU - Mahmoud Elansary AU - Kyle Kai-How Farh AU - Andre Franke AU - Ann-Stephan Gori AU - Philippe Goyette AU - Jonas Halfvarson AU - Talin Haritunians AU - Jo Knight AU - Ian C Lawrance AU - Charlie W Lees AU - Edouard Louis AU - Rob Mariman AU - Theo Meuwissen AU - Myriam Mni AU - Yukihide Momozawa AU - Miles Parkes AU - Sarah L Spain AU - Emilie Théâtre AU - Gosia Trynka AU - Jack Satsangi AU - Suzanne van Sommeren AU - Severine Vermeire AU - Ramnik J Xavier AU - International IBD Genetics Consortium AU - Rinse K Weersma AU - Richard H Duerr AU - Christopher G Mathew AU - John D Rioux AU - Dermot PB McGovern AU - Judy H Cho AU - Michel Georges AU - Mark J Daly AU - Jeffrey C Barrett Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/10/20/028688.abstract N2 - Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder that affects millions worldwide. Genome-wide association studies (GWAS) have identified 200 IBD-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 IBD loci using high-density genotyping in 67,852 individuals. Of the 139 independent associations identified in these regions, 18 were pinpointed to a single causal variant with >95% certainty, and an additional 27 associations to a single variant with >50% certainty. These 45 variants are significantly enriched for protein-coding changes (n=13), direct disruption of transcription factor binding sites (n=3) and tissue specific epigenetic marks (n=10), with the latter category showing enrichment in specific immune cells among associations stronger in CD and gut mucosa among associations stronger in UC. The results of this study suggest that high-resolution, fine-mapping in large samples can convert many GWAS discoveries into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms. ER -