Year: 2018
Type: dissertation
Study design: Observational Study
Abstract: Objective: Fibrostenosis is a complication of Crohn's disease (CD) occurring in at least 30% of patients.Attempts to identify genetic markers for fibrostenotic CD were hampered by poor and subjective characterization of the study population.The aim of this study was to identify genetic markers by focussing on early, well-defined fibrostenotic CD.Design: In this multicenter, retrospective, nested case-control association study, early ileal fibrostenotic CD was defined based on computed tomography or magnetic resonance enterography and occurring within five years following diagnosis.The control cohort consisted of ileal CD patients without fibrostenotic or penetrating complications for a minimum of ten years.Associations were assessed using Immunochip, and positive associations were evaluated in a replication cohort.Results: Based on logistic regression and multiple logistic regression correcting for disease location, eight SNPs reached the 10 -5 significance level in the discovery cohort, and two could be validated in the replication cohort.Meta-analysis revealed nine associated loci, which were used to calculate a genetic risk score (GRS) for each individual.Using a cut-off based on the AUC (0.885) in the discovery cohort, a positive predictive value of 54% and a negative predictive value of 69% was reached to predict early fibrostenosis in the validation dataset.The time to development of fibrostenosis was significantly linked with the GRS, with a 5-year fibrostenosis rate of 38% in patients with a high GRS compared with 4% in the low GRS group.Conclusion: This carefully phenotyped association study reveals an important genetic contribution to the early development of fibrostenosis in ileal CD.
Author: Tom Holvoet
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2901893419