title: Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease.
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.
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: James C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Daniele
authors.initials: D
authors.lastname: Biasci
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Roberts
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Gearry
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Mansfield
authors.affiliation: University of Exeter Medical School, Exeter, UK.
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Department of Medical and Molecular Genetics, Faculty of Life Science and Medicine, King's College London, London, UK.
authors.forename: Natalie J
authors.identifier: http://orcid.org/0000-0002-5901-7371
authors.initials: NJ
authors.lastname: Prescott
authors.affiliation: Gastrointestinal Unit, Division of Medical Sciences, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
authors.affiliation: Paediatric Gastroenterology and Nutrition, Child Life and Health, College of Medicine and Veterinary Medicine, University of Edinburgh, Royal Hospital for Sick Children, Edinburgh, UK.
authors.forename: David C
authors.identifier: http://orcid.org/0000-0003-0879-1129
authors.initials: DC
authors.lastname: Wilson
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Jostins
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Anderson
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: James A
authors.identifier: http://orcid.org/0000-0002-6003-8559
authors.initials: JA
authors.lastname: Traherne
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Miles
authors.initials: M
authors.lastname: Parkes
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D016678:Genome / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis