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

James C. Lee*, Daniele Biasci, Rebecca Roberts, Richard B. Gearry, John C. Mansfield, Tariq Ahmad, Natalie J. Prescott, Jack Satsangi, David C. Wilson, Luke Jostins, Carl A. Anderson, James A. Traherne, Paul A. Lyons, Miles Parkes, Kenneth G C Smith

*Corresponding author for this work

Research output: Contribution to journalLetterpeer-review

201 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)262-268
Number of pages7
JournalNature Genetics
Volume49
Issue number2
Early online date9 Jan 2017
DOIs
Publication statusPublished - Feb 2017

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