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IntroductionThe joint associations across genetic risk, modifiable lifestyle factors, and inflammatory bowel disease (IBD) remains unclear.MethodsGenetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into high, intermediate, and low genetic risk categories. Weighted healthy lifestyle scores were constructed based on 5 common lifestyle factors and categorized into favorable (4 or 5 healthy lifestyle factors), intermediate (3 healthy lifestyle factors), and unfavorable (0-2 healthy lifestyle factors) groups. Cox proportional hazards regression model was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for their associations.ResultsDuring the 12-year follow-up, 707 cases with CD and 1576 cases with UC were diagnosed in the UK Biobank cohort. Genetic risk and unhealthy lifestyle categories were monotonically associated with CD and UC risk with no multiplicative interaction between them. The HR of CD and UC were 2.24 (95% CI 1.75-2.86) and 2.15 (95% CI 1.82-2.53) for those with a high genetic risk, respectively. The HR of CD and UC for individuals with an unfavorable lifestyle were 1.94 (95% CI 1.61-2.33) and 1.98 (95% CI 1.73-2.27), respectively. The HR of individuals with a high genetic risk but a favorable lifestyle (2.33, 95% CI 1.58-3.44 for CD, and 2.05, 95% CI 1.58-2.66 for UC) were reduced nearly by half, compared with those with a high genetic risk but an unfavorable lifestyle (4.40, 95% CI 2.91-6.66 for CD and 4.44, 95% CI 3.34-5.91 for UC).DiscussionGenetic and lifestyle factors were independently associated with susceptibility to incident CD and UC. Adherence to a favorable lifestyle was associated with a nearly 50% lower risk of CD and UC among participants at a high genetic risk.

Original publication

DOI

10.14309/ajg.0000000000002180

Type

Journal

The American journal of gastroenterology

Publication Date

03/2023

Volume

118

Pages

511 - 522

Addresses

Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Keywords

Humans, Colitis, Ulcerative, Inflammatory Bowel Diseases, Crohn Disease, Incidence, Risk Factors, Prospective Studies, Life Style, Adult