Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease
Open accessAbstract
For most immune-mediated diseases, the main determinant of patient well-being is not the diagnosis itself but instead the course that the disease takes over time (prognosis). Prognosis may vary substantially between patients for reasons that are poorly understood. Familial studies support a genetic contribution to prognosis, but little evidence has been found for a proposed association between prognosis and the burden of susceptibility variants. To better characterize how genetic variation influences disease prognosis, we performed a within-cases genome-wide association study in two cohorts of patients with Crohn's disease. We identified four genome-wide significant loci, none of which showed any association with disease susceptibility. Conversely, the aggregated effect of all 170 disease susceptibility loci was not associated with disease prognosis. Together, these data suggest that the genetic contribution to prognosis in Crohn's disease is largely independent of the contribution to disease susceptibility and point to a biology of prognosis that could provide new therapeutic opportunities.
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- Authors
- Lee, J. C., Biasci, D., Roberts, R., Gearry, R. B., Mansfield, J. C., Ahmad, T., Prescott, N. J., Satsangi, J., Wilson, D. C., Jostins, L., Anderson, C. A., UK IBD Genetics Consortium, Traherne, J. A., Lyons, P. A., Parkes, M., & Smith, K. G. C.
- Affiliations
- University of Cambridge (GB)
- University of Otago (NZ)
- Newcastle University (GB)
- University of Exeter (GB)
- King's College London (GB)
- Western General Hospital (GB)
- Royal Hospital for Sick Children (GB)
- Centre for Human Genetics (GB)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Lee, James C
- Smith, Kenneth G C
- ORCID
- Venue
- Nature Genetics
- Published
- 2017-01-09
- Volume
- 49
- Issue
- 2
- Pages
- 262-268
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5730041
- OpenAlex
- W2570178861
- Cited by
- 304
- References
- 53
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 20 · 2023: 29 · 2022: 24 · 2021: 26 · 2020: 66 · 2019: 50 · 2018: 41 · 2017: 18
- FWCI
- 31.69
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Apollo
- Funders
- Wellcome Trust (102974/Z/13/Z, 094491/Z/10/Z, UK10K, 105920/Z/14/Z, WT091310, 098051)
- Cancer Research UK (20406)
- National Institute for Health and Care Research (NF-SI-0514-10109, NIHR-RP-R3-12-026)
- European Commission (238756)
- Crohn's and Colitis UK (M14-2, M14-5, M11-1)
- Evelyn Trust
- Medical Research Council (MR/M00533X/1, 098051, MR/L019027/1, MR/L019027, MC_UU_00008/7)
- NIHR Cambridge Biomedical Research Centre
- H2020 European Research Council (695551)
- FP7 People: Marie-Curie Actions
- 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, disease prognosis, disease severity, disease susceptibility loci, genetic loci, immune-mediated diseases, clinical course
- MeSH terms
- Crohn Disease, Female, Genotype, Humans, Male, Prognosis, Genome, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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