Journal
NATURE GENETICS
Volume 49, Issue 2, Pages 262-268Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3755
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Funding
- NIHR Biomedical Research Centres in Cambridge and Guy's and St Thomas'
- Crohn's and Colitis UK (Medical Research Award) [M/14/2]
- Evelyn Trust [17/07]
- Medical Research Council [MR/L019027/1]
- Wellcome Trust Intermediate Clinical Fellowship [105920/Z/14/Z]
- Marie Curie PhD Fellowship (TranSVIR) [FP7-PEOPLE-ITN-2008 238756]
- Wellcome Trust University Award [094491/Z/10/Z]
- European Research Council [695551]
- Wellcome Trust [098051, WT091310]
- Wellcome Trust [094491/Z/10/Z] Funding Source: Wellcome Trust
- Cancer Research UK
- Versus Arthritis [20406] Funding Source: researchfish
- Chief Scientist Office [ETM/137] Funding Source: researchfish
- Crohn's and Colitis UK [M11-1, M14-2, M14-5] Funding Source: researchfish
- Medical Research Council [MR/M00533X/1, G0800675, G0600329, MC_UU_00008/7, MR/L019027/1, G0800759, MC_UU_12010/7] Funding Source: researchfish
- Medical Research Foundation [C0482] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10109, NIHR-RP-R3-12-026] Funding Source: researchfish
- Wellcome Trust [102974/Z/13/Z] Funding Source: researchfish
- MRC [MC_UU_12010/7, MC_UU_00008/7, G0800759, MR/L019027/1, MR/M00533X/1, G0600329, G0800675] Funding Source: UKRI
- European Research Council (ERC) [695551] Funding Source: European Research Council (ERC)
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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)(1-3). Prognosis may vary substantially between patients for reasons that are poorly understood. Familial studies support a genetic contribution to prognosis(4-6), but little evidence has been found for a proposed association between prognosis and the burden of susceptibility variants(7-13). 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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