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Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Lookup NU author(s): Dr John Mansfield

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Abstract

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 x 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.


Publication metadata

Author(s): Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, Taylor KD, Lee JC, Goyette P, Imielinski M, Latiano A, Lagace C, Scott R, Amininejad L, Bumpstead S, Baidoo L, Baldassano RN, Barclay M, Bayless TM, Brand S, Buning C, Colombel JF, Denson LA, De Vos M, Dubinsky M, Edwards C, Ellinghaus D, Fehrmann RSN, Floyd JAB, Florin T, Franchimont D, Franke L, Georges M, Glas J, Glazer NL, Guthery SL, Haritunians T, Hayward NK, Hugot JP, Jobin G, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, McGovern DP, Milla M, Montgomery GW, Morley KI, Mowat C, Ng A, Newman W, Ophoff RA, Papi L, Palmieri O, Peyrin-Biroulet L, Panes J, Phillips A, Prescott NJ, Proctor DD, Roberts R, Russell R, Rutgeerts P, Sanderson J, Sans M, Schumm P, Seibold F, Sharma Y, Simms LA, Seielstad M, Steinhart AH, Targan SR, van den Berg LH, Vatn M, Verspaget H, Walters T, Wijmenga C, Wilson DC, Westra HJ, Xavier RJ, Zhao ZZ, Ponsioen CY, Andersen V, Torkvist L, Gazouli M, Anagnou NP, Karlsen TH, Kupcinskas L, Sventoraityte J, Mansfield JC, Kugathasan S, Silverberg MS, Halfvarson J, Rotter JI, Mathew CG, Griffiths AM, Gearry R, Ahmad T, Brant SR, Chamaillard M, Satsangi J, Cho JH, Schreiber S, Daly MJ, Barrett JC, Parkes M, Annese V, Hakonarson H, Radford-Smith G, Duerr RH, Vermeire S, Weersma RK, Rioux JD

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2011

Volume: 43

Issue: 3

Pages: 246-252

Print publication date: 06/02/2011

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng.764

DOI: 10.1038/ng.764


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Funding

Funder referenceFunder name
European Community
German Ministry of Education and Research through the National Genome Research Network
Helmsley Foundation
Italian Group for IBD
National Association for Colitis and Crohn's disease
Primary Children's Medical Center Foundation
Royal Brisbane and Women's Hospital Foundation
Adessium Foundation
Amyotrophic Lateral Sclerosis Association
Cedars-Sinai Medical Center
Crohn's and Colitis Foundation of America
Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition
Medical Research Council UK
National Health and Medical Research Council, Australia
National Institute for Health Research (NIHR) Biomedical Research Centre
Peninsular College of Medicine and Dentistry, Exeter
Prinses Beatrix Fonds
Programme Hospitalier de Recherche Clinique
University of Queensland
083948/Z/07/ZWellcome Trust
916.10.135NWO (ZonMW)
918.66.620Netherlands Organization for Scientific Research (NWO)
93519031Netherlands Genomics Initiative
90.700.281Netherlands Organization for Scientific Research (NWO)
AI062773
DK062413
DK062420
DK062422
DK062423
DK062432
DK069513
DK076984
DK084554
DK83756
BR 1912/5-1Deutsche Forschungsgemeinschaft (DFG)
BSIK03009Celiac Disease Consortium
DK 063491NIH/NIDDK
DK043351
DK062429
DK062431
DK064869US National Institutes of Health (NIH)/NIDDK
M01-RR00425National Center for Research Resources (NCRR)
P01-DK046763NIH/NIDDK
P50/05/EKMS05/62Else Kroner-Fresenius-Stiftung
WT089120/Z/09/ZWellcome Trust
WT091745/Z/10/ZWellcome Trust

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