An Envirogenomic Signature Is Associated with Risk of IBD-Related Surgery in a Population-Based Crohn’s Disease Cohort

Abstract

Background and AimsCrohn’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. MethodsWe 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. ResultsA 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. ConclusionsThe 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.