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Nat Genet. 2017 Feb;49(2):262-268. doi: 10.1038/ng.3755. Epub 2017 Jan 9.

Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease.

Author information

1
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
2
Department of Medicine, University of Otago, Christchurch, New Zealand.
3
Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
4
University of Exeter Medical School, Exeter, UK.
5
Department of Medical and Molecular Genetics, Faculty of Life Science and Medicine, King's College London, London, UK.
6
Gastrointestinal Unit, Division of Medical Sciences, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
7
Paediatric Gastroenterology and Nutrition, Child Life and Health, College of Medicine and Veterinary Medicine, University of Edinburgh, Royal Hospital for Sick Children, Edinburgh, UK.
8
Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK.
9
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
10
Department of Pathology, University of Cambridge, Cambridge, UK.

Abstract

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.

Comment in

PMID:
28067912
PMCID:
PMC5730041
DOI:
10.1038/ng.3755
[Indexed for MEDLINE]
Free PMC Article

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