Huang, HailiangFang, MingJostins, LukeMirkov, Maša UmićevićBoucher, GabrielleAnderson, Carl AAndersen, VibekeCleynen, IsabelleCortes, AdrianCrins, FrançoisD'Amato, MauroDeffontaine, ValérieDimitrieva, JuliaDocampo, ElisaElansary, MahmoudFarh, Kyle Kai-HowFranke, AndreGori, Ann-StephanGoyette, PhilippeHalfvarson, JonasHaritunians, TalinKnight, JoLawrance, Ian CLees, Charlie WLouis, EdouardMariman, RobMeuwissen, TheoMni, MyriamMomozawa, YukihideParkes, MilesSpain, Sarah LThéâtre, EmilieTrynka, GosiaSatsangi, Jackvan Sommeren, SuzanneVermeire, SeverineXavier, RamnikWeersma, Rinse KDuerr, Richard HMathew, Christopher GRioux, John DMcGovern, Dermot PBCho, Judy HGeorges, MichelDaly, MarkBarrett, Jeffrey C2018-01-182017Huang, H., M. Fang, L. Jostins, M. U. Mirkov, G. Boucher, C. A. Anderson, V. Andersen, et al. 2017. “Fine-mapping inflammatory bowel disease loci to single variant resolution.” Nature 547 (7662): 173-178. doi:10.1038/nature22969. http://dx.doi.org/10.1038/nature22969.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34651928Summary The inflammatory bowel diseases (IBD) are chronic gastrointestinal inflammatory disorders that affect millions worldwide. Genome-wide association studies 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. We pinpointed 18 associations 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 in 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.en-USJournal Article2018-01-1810.1038/nature22969