Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
Open accessAbstract
We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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The large-scale impact of large numbers of common variants may be a general feature of human complex traits.
“Indeed, the large-scale impact of large numbers of common variants may be a general feature of human complex traits 70–77”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [73]
Hypothesized genetic architectures consisting entirely of rare variants are inconsistent with the data for AD, ASD, BIP, and SCZ (as well as for multiple other complex biomedical diseases).
“Hypothesized genetic architectures consisting entirely of rare variants are inconsistent with the data for AD, ASD, BIP, and SCZ (as well as for multiple other complex biomedical diseases). 70–77”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [73]
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- Authors
- Franke, A., McGovern, D. P. B., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., Lees, C. W., Balschun, T., Lee, J., Roberts, R., Anderson, C. A., Bis, J. C., Bumpstead, S., Ellinghaus, D., Festen, E. M., Georges, M., Green, T., Haritunians, T., Jostins, L., Latiano, A., Mathew, C. G., Montgomery, G. W., Prescott, N. J., Raychaudhuri, S., Rotter, J. I., Schumm, P., Sharma, Y., Simms, L. A., Taylor, K. D., Whiteman, D., Wijmenga, C., Baldassano, R. N., Barclay, M., Bayless, T. M., Brand, S., Büning, C., Cohen, A., Colombel, J.-F., Cottone, M., Stronati, L., Denson, T., De Vos, M., D'Inca, R., Dubinsky, M., Edwards, C., Florin, T., Franchimont, D., Gearry, R., Glas, J., Van Gossum, A., Guthery, S. L., Halfvarson, J., Verspaget, H. W., Hugot, J.-P., Karban, A., Laukens, D., Lawrance, I., Lemann, M., Levine, A., Libioulle, C., Louis, E., Mowat, C., Newman, W., Panés, J., Phillips, A., Proctor, D. D., Regueiro, M., Russell, R., Rutgeerts, P., Sanderson, J., Sans, M., Seibold, F., Steinhart, A. H., Stokkers, P. C. F., Torkvist, L., Kullak-Ublick, G., Wilson, D., Walters, T., Targan, S. R., Brant, S. R., Rioux, J. D., D'Amato, M., Weersma, R. K., Kugathasan, S., Griffiths, A. M., Mansfield, J. C., Vermeire, S., Duerr, R. H., Silverberg, M. S., Satsangi, J., Schreiber, S., Cho, J. H., Annese, V., Hakonarson, H., Daly, M. J., & Parkes, M.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Wellcome Sanger Institute (GB)
- Children's Hospital of Philadelphia (US)
- Peninsula College of Medicine and Dentistry (GB)
- Western General Hospital (GB)
- Christian-Albrechts-Universität zu Kiel (DE)
- University of Cambridge (GB)
- University of Otago (NZ)
- University of Washington (US)
- University Medical Center Groningen (NL)
- University of Liège (BE)
- Harvard University (US)
- Casa Sollievo della Sofferenza (IT)
- Guy's Hospital (GB)
- QIMR Berghofer Medical Research Institute (AU)
- Yale University (US)
- Johns Hopkins University (US)
- Ludwig-Maximilians-Universität München (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Jewish General Hospital (CA)
- Université de Lille (FR)
- Ospedale Vincenzo Cervello (IT)
- National Agency for New Technologies, Energy and Sustainable Economic Development (IT)
- Cincinnati Children's Hospital Medical Center (US)
- Torbay Hospital (GB)
- Mater Health Services (AU)
- Université Libre de Bruxelles (BE)
- University of Utah (US)
- Örebro University Hospital (SE)
- Leiden University Medical Center (NL)
- Université Paris Diderot (FR)
- Technion – Israel Institute of Technology (IL)
- Ghent University Hospital (BE)
- The University of Western Australia (AU)
- Tel Aviv University (IL)
- Ninewells Hospital (GB)
- University of Manchester (GB)
- Hospital Clínic de Barcelona (ES)
- University of Pittsburgh (US)
- Universitair Ziekenhuis Leuven (BE)
- National Health Service (GB)
- University of Bern (CH)
- Mount Sinai Hospital (CA)
- Amsterdam UMC Location University of Amsterdam (NL)
- University Hospital Zurich (CH)
- University of Edinburgh (GB)
- University of Toronto (CA)
- Montreal Heart Institute (CA)
- Emory University (US)
- Newcastle University (GB)
- Corresponding author
- Parkes, Miles
- ORCID
- McGovern, Dermot P B
- Barrett, Jeffrey C
- Ahmad, Tariq
- Lees, Charlie W
- Lee, James
- Anderson, Carl A
- Bis, Joshua C
- Ellinghaus, David
- Georges, Michel
- Haritunians, Talin
- Latiano, Anna
- Mathew, Christopher G
- Montgomery, Grant W
- Prescott, Natalie J
- Raychaudhuri, Soumya
- Rotter, Jerome I
- Sharma, Yashoda
- Simms, Lisa A
- Taylor, Kent D
- Whiteman, David
- Wijmenga, Cisca
- Baldassano, Robert N
- Barclay, Murray
- Brand, Stephan
- Cottone, Mario
- Stronati, Laura
- Dubinsky, Marla
- Edwards, Cathryn
- Franchimont, Denis
- Gearry, Richard
- Halfvarson, Jonas
- Verspaget, Hein W
- Hugot, Jean-Pierre
- Laukens, Debby
- Levine, Arie
- Louis, Edouard
- Mowat, Craig
- Newman, William
- Panés, Julián
- Regueiro, Miguel
- Russell, Richard
- Sanderson, Jeremy
- Sans, Miquel
- Seibold, Frank
- Steinhart, A Hillary
- Stokkers, Pieter C F
- Kullak-Ublick, Gerd
- Walters, Thomas
- Targan, Stephan R
- Brant, Steven R
- Rioux, John D
- Weersma, Rinse K
- Kugathasan, Subra
- Griffiths, Anne M
- Mansfield, John C
- Duerr, Richard H
- Silverberg, Mark S
- Schreiber, Stefan
- Cho, Judy H
- Annese, Vito
- Hakonarson, Hakon
- Daly, Mark J
- Parkes, Miles
- Venue
- Nature Genetics
- Published
- 2010-11-21
- Volume
- 42
- Issue
- 12
- Pages
- 1118-1125
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3299551
- OpenAlex
- W2106779017
- Cited by
- 2,520
- References
- 52
- Citations by year
- 2026: 38 · 2025: 69 · 2024: 94 · 2023: 104 · 2022: 93 · 2021: 108 · 2020: 121 · 2019: 150 · 2018: 154 · 2017: 196 · 2016: 210 · 2015: 214 · 2014: 239 · 2013: 255 · 2012: 276
- FWCI
- 24.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- PubMed Central (acceptedVersion)
- ORBi (University of Liège) (submittedVersion, other-oa)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Crohn's and Colitis Foundation of America (DK062422)
- Abbott Laboratories
- Wellcome Trust (089120, WT089120/Z/09/Z)
- Crohn's and Colitis Foundation
- Cedars-Sinai Medical Center
- Action Medical Research
- National Institute for Health and Care Research
- King's College London
- Deutsche Forschungsgemeinschaft
- Fonds De La Recherche Scientifique - FNRS
- Fonds Wetenschappelijk Onderzoek
- Exzellenzclusters Entzündungsforschung
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc045133-001, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01hc085085-011, n01hc085083-027, n01hc085080-026, n01hc085086-022, n01hc075150-004, n01hc035129-010, n01hc055222-001, N01HC85086, M01-RR00425, N01HC85079, DK062429, RR00425, N01-HC-75150, N01HC-35129, N01HC-15103, N01-HC-45133, DK046763, HL080295)
- Medical Research Council (G0800759, G0800675)
- National Health and Medical Research Council
- National Heart, Lung, and Blood Institute (N01-HC-85081, N01HC85085, N01 HC085086, N01HC-85083, DK062429, N01HC15103, N01 HC085079, HL-087652, N01HC85082, N01HC‐75150, N01 HC85086, R01HL087652, N01 HC035129, N01HC85080, N01 HC015103, N01 HC55222, N01‐HC‐45133, U01HL080295, N01 HC055222, HL080295, N01 HC075150, DK062422, N01 HC045133, N01-HC85079, N01-HC85084, N01HC35129)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, DK-06-2423, DK76984, P01DK046763, DK062429, DK062413, DK062420, R21DK084554, DK064869, R03DK076984, DK062431, DK062422, K23DK069513, DK062432, DK046763, DK 069513, DK084554, R01DK064869, U01DK062420, M01-RR00425, U01DK062429, U24DK062429, U01DK062413, U01DK062422, P30DK063491, U01DK062432, P30DK043351, U01DK062431, U01DK062423)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR055688)
- National Center for Research Resources (M01RR000425, M01-RR00425)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- Crohn's disease, inflammatory bowel disease, genetic susceptibility loci, candidate genes, Smad3, ERAP2, IL-10, IL2RA, TYK2, FUT2, DNMT3A, BACH2, TAGAP, pathogenesis
- MeSH terms
- Crohn Disease, Humans, Genetic Linkage, Genetic Variation, Reproducibility of Results, Genome, Human, Computational Biology, Genetic Predisposition to Disease, Genome-Wide Association Study, Genetic Loci
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