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

Lookup NU author(s): Dr John Mansfield


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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.

Publication metadata

Author(s): Lee JC, Biasci D, Roberts R, Gearry RB, Mansfield JC, Ahmad T, Prescotts NJ, Satsangi J, Wilson DC, Jostins L, Anderson CA, UK IBD Genetics Consortium, Traherne JA, Lyons PA, Parkes M, Smith KGC

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2017

Volume: 49

Issue: 2

Pages: 262-268

Print publication date: 01/02/2017

Online publication date: 09/01/2017

Acceptance date: 29/11/2016

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group


DOI: 10.1038/ng.3755


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