Association mapping of inflammatory bowel disease loci to single variant resolution
Maša Umićević Mirkov,
Carl A. Anderson,
Kyle Kai-How Farh,
Ian C Lawrance,
Charlie W Lees,
Sarah L. Spain,
Suzanne van Sommeren,
Ramnik J. Xavier,
International IBD Genetics Consortium,
Rinse K. Weersma,
Richard H Duerr,
Christopher G. Mathew,
John D Rioux,
Dermot P.B. McGovern,
Judy H Cho,
Jeffrey C Barrett
Posted 08 Oct 2015
bioRxiv DOI: 10.1101/028688 (published DOI: 10.1038/nature22969)
Posted 08 Oct 2015
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.
- Downloaded 3,591 times
- Download rankings, all-time:
- Site-wide: 2,986
- In genetics: 120
- Year to date:
- Site-wide: 39,821
- Since beginning of last month:
- Site-wide: 52,460
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!