Unraveling Genetic Versus Environmental Factors Determining Disease Course in Inflammatory Bowel Diseases: A Population-Based Cohort Study in First- and Second-Generation Immigrants

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BACKGROUND: Inflammatory bowel diseases (IBD) incidence in immigrants approximates that of the host country in progressive generations but less is known about their disease outcome. We investigate how the immigrant generation affects IBD outcomes. METHODS: In this population-based cohort study, the risks of first IBD-related hospitalization, first IBD-related surgery, need for advanced therapies, and perianal disease were compared between first- and second-generation immigrants (stratified into Western/non-Western) and native Danes, using Cox proportional hazard regression to estimate adjusted hazard ratios (aHRs), correcting for sex, age at IBD diagnosis, and calendar year of IBD diagnosis. RESULTS: First-generation immigrants had lower risk of IBD-related surgery (aHRWestern 0.89; 95% confidence interval [CI] 0.75-1.05, aHRnon-Western 0.79; 95% CI, 0.67-0.92) and advanced therapy (aHRWestern 0.87; 95% CI, 0.77-0.99, aHRnon-Western 0.83; 95% CI, 0.74-0.94) than native Danes, whereas second-generation immigrants resembled native Danes. However, second-generation immigrants had higher risk of hospitalization than native Danes (aHRWestern 1.28; 95% CI, 1.05-1.55, aHRnon-Western 1.40; 95% CI, 1.28-1.54), whereas in first-generation immigrants this was only observed in non-Western ulcerative colitis patients (aHR 1.19; 95% CI, 1.08-1.32). Across both generations, non-Western immigrants had higher risk of perianal disease (Crohn's disease: aHRfirst-generation 1.55; 95% CI, 1.25-1.92; aHRsecond-generation 1.58; 95% CI, 1.25-2.01). CONCLUSIONS: Disease outcomes change across immigrant generations, pointing to environmental factors possibly impacting disease course, which needs further investigation. In contrast, non-Western immigrants were shown to have more perianal disease in both generations, suggesting a genetic susceptibility for this debilitating phenotype.

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