RT Journal Article
SR Electronic
T1 Association mapping of inflammatory bowel disease loci to single variant resolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 028688
DO 10.1101/028688
A1 Hailiang Huang
A1 Ming Fang
A1 Luke Jostins
A1 Maša Umićević Mirkov
A1 Gabrielle Boucher
A1 Carl A Anderson
A1 Vibeke Andersen
A1 Isabelle Cleynen
A1 Adrian Cortes
A1 François Crins
A1 Mauro D’Amato
A1 Valérie Deffontaine
A1 Julia Dimitrieva
A1 Elisa Docampo
A1 Mahmoud Elansary
A1 Kyle Kai-How Farh
A1 Andre Franke
A1 Ann-Stephan Gori
A1 Philippe Goyette
A1 Jonas Halfvarson
A1 Talin Haritunians
A1 Jo Knight
A1 Ian C Lawrance
A1 Charlie W Lees
A1 Edouard Louis
A1 Rob Mariman
A1 Theo Meuwissen
A1 Myriam Mni
A1 Yukihide Momozawa
A1 Miles Parkes
A1 Sarah L Spain
A1 Emilie Théâtre
A1 Gosia Trynka
A1 Jack Satsangi
A1 Suzanne van Sommeren
A1 Severine Vermeire
A1 Ramnik J Xavier
A1 International IBD Genetics Consortium
A1 Rinse K Weersma
A1 Richard H Duerr
A1 Christopher G Mathew
A1 John D Rioux
A1 Dermot PB McGovern
A1 Judy H Cho
A1 Michel Georges
A1 Mark J Daly
A1 Jeffrey C Barrett
YR 2015
UL http://biorxiv.org/content/early/2015/10/08/028688.abstract
AB 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.