An Envirogenomic Signature Is Associated with Risk of IBD-Related Surgery in a Population-Based Crohn’s Disease Cohort
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Background and Aims
Crohn’s disease (CD) is an inflammatory bowel disease (IBD) caused by a combination of genetic, clinical, and environmental factors. Identification of CD patients at high risk of requiring surgery may assist clinicians to decide on a top–down or step-up treatment approach.
We conducted a retrospective case–control analysis of a population-based cohort of 503 CD patients. A regression-based data reduction approach was used to systematically analyse 63 genomic, clinical and environmental factors for association with IBD-related surgery as the primary outcome variable.
A multi-factor model was identified that yielded the highest predictive accuracy for need for surgery. The factors included in the model were the NOD2 genotype (OR = 1.607, P = 2.3 × 10−5), having ever had perianal disease (OR = 2.847, P = 4 × 10−6), being post-diagnosis smokers (OR = 6.312, P = 7.4 × 10−3), being an ex-smoker at diagnosis (OR = 2.405, P = 1.1 × 10−3) and age (OR = 1.012, P = 4.4 × 10−3). Diagnostic testing for this multi-factor model produced an area under the curve of 0.681 (P = 1 × 10−4) and an odds ratio of 3.169, (95 % CI P = 1 × 10−4) which was higher than any factor considered independently.
The results of this study require validation in other populations but represent a step forward in the development of more accurate prognostic tests for clinicians to prescribe the most optimal treatment approach for complicated CD patients.
KeywordsNOD2 genotype Smoking Perianal disease
Declaration of Funding Sources
Financial assistance for this project was provided by the Griffith Health Institute. Bushra Farah Nasir is supported by an Australian Postgraduate Stipend
Conflict of Interest
The authors declare no conflict of interest.
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