Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
Open accessAbstract
Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development.
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The G allele of rs744166 in STAT3 is associated with increased risk in MS and decreased risk in Crohn's disease.
“One example is rs744166 (located in an intron of the STAT3 gene on chromosome 17): the G allele is associated with increased risk in MS38 and decreased risk in Crohn's disease.71”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [71]
Using a standard liability threshold model, the previously reported loci combined with the new loci discovered in this study explain ∼39% of the total variance (or 55% of the heritability) of advanced AMD.
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- Authors
- the NIDDK IBD Genetics Consortium, Barrett, J. C., the Belgian-French IBD Consortium, the Wellcome Trust Case Control Consortium, Hansoul, S., Nicolae, D. L., Cho, J. H., Duerr, R. H., Rioux, J. D., Brant, S. R., Silverberg, M. S., Taylor, K. D., Barmada, M. M., Bitton, A., Dassopoulos, T., Datta, L. W., Green, T., Griffiths, A. M., Kistner, E. O., Murtha, M. T., Regueiro, M. D., Rotter, J. I., Schumm, L. P., Steinhart, A. H., Targan, S. R., Xavier, R. J., Libioulle, C., Sandor, C., Lathrop, M., Belaiche, J., Dewit, O., Gut, I., Heath, S., Laukens, D., Mni, M., Rutgeerts, P., Van Gossum, A., Zelenika, D., Franchimont, D., Hugot, J.-P., de Vos, M., Vermeire, S., Louis, E., Cardon, L. R., Anderson, C. A., Drummond, H., Nimmo, E., Ahmad, T., Prescott, N. J., Onnie, C. M., Fisher, S. A., Marchini, J., Ghori, J., Bumpstead, S., Gwilliam, R., Tremelling, M., Deloukas, P., Mansfield, J., Jewell, D., Satsangi, J., Mathew, C. G., Parkes, M., Georges, M., & Daly, M. J.
- Affiliations
- Centre for Human Genetics (GB)
- University of Liège (BE)
- University of Chicago (US)
- Yale University (US)
- University of Pittsburgh (US)
- Broad Institute (US)
- Johns Hopkins University (US)
- Mount Sinai Hospital (CA)
- Cedars-Sinai Medical Center (US)
- Royal Victoria Hospital (CA)
- University of Toronto (CA)
- Harvard University (US)
- Cliniques Universitaires Saint-Luc (BE)
- Ghent University Hospital (BE)
- Universitair Ziekenhuis Leuven (BE)
- Erasmus Hospital (BE)
- Inserm (FR)
- Western General Hospital (GB)
- University of Exeter (GB)
- Guy's Hospital (GB)
- University of Oxford (GB)
- Wellcome Sanger Institute (GB)
- University of Cambridge (GB)
- Royal Victoria Infirmary (GB)
- Corresponding author
- Daly, Mark J
- ORCID
- Barrett, Jeffrey C
- Nicolae, Dan L
- Cho, Judy H
- Duerr, Richard H
- Rioux, John D
- Brant, Steven R
- Silverberg, Mark S
- Taylor, Kent D
- Barmada, M Michael
- Bitton, Alain
- Dassopoulos, Themistocles
- Griffiths, Anne M
- Regueiro, Miguel D
- Rotter, Jerome I
- Schumm, L Philip
- Steinhart, A Hillary
- Targan, Stephan R
- Xavier, Ramnik J
- Libioulle, Cécile
- Sandor, Cynthia
- Lathrop, Mark
- Dewit, Olivier
- Gut, Ivo
- Heath, Simon
- Laukens, Debby
- Franchimont, Denis
- Hugot, Jean-Pierre
- Louis, Edouard
- Anderson, Carl A
- Ahmad, Tariq
- Prescott, Natalie J
- Fisher, Sheila A
- Marchini, Jonathan
- Deloukas, Panos
- Mansfield, John
- Mathew, Christopher G
- Parkes, Miles
- Georges, Michel
- Daly, Mark J
- Venue
- Nature Genetics
- Published
- 2008-06-29
- Volume
- 40
- Issue
- 8
- Pages
- 955-962
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2574810
- OpenAlex
- W2165872127
- Cited by
- 2,593
- References
- 51
- Citations by year
- 2026: 19 · 2025: 37 · 2024: 68 · 2023: 63 · 2022: 61 · 2021: 81 · 2020: 84 · 2019: 104 · 2018: 114 · 2017: 116 · 2016: 121 · 2015: 131 · 2014: 173 · 2013: 219 · 2012: 247
- FWCI
- 29.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- ORBi (University of Liège) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust (068545/Z/02), 068545)
- National Institute of Allergy and Infectious Diseases (AI06277, R01AI062773)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK62432, DK62431, DK064869, DK62423, DK62413, DK62422, R01DK064869, DK62420, DK62429, U01DK062420, U01DK062429, U24DK062429, U01DK062413, U01DK062422, P30DK063491, U01DK062432, U01DK062431, P30DK040561, U01DK062423)
- 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, genetic susceptibility loci, genome-wide association study, meta-analysis, replication, STAT3, JAK2, ICOSLG, CDKAL1, intelectin-1, inflammatory bowel disease genetics, gene discovery
- MeSH terms
- Crohn Disease, Humans, Genome, Human, Genetic Predisposition to Disease, Quantitative Trait Loci
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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