Associations of genetic risk and modifiable lifestyle factors with comorbid psoriasis and Crohns disease

Abstract

Background Psoriasis and Crohn disease (CD) are epidemiologically associated with each other. The contribution of genetics and modifiable lifestyle factors to the development of comorbid disease is unclear. Objectives To investigate the associations between polygenic risk score (PRS) and modifiable lifestyle factors and the development of comorbid psoriasis and CD. Methods This is a prospective cohort study utilizing PRS and survey data on modifiable lifestyle factors. We examined their associations with the development of comorbid psoriasis and CD in patients of European ancestry in the UK Biobank. Kaplan–Meier survival analysis and multivariable Cox proportional hazards regression models were used to evaluate the association between the studied variables and the risk of comorbid disease development. Results The study included 430 758 participants, with 124 cases (comorbid psoriasis and CD) and 430 634 controls. A significant difference (P < 0.001; log-rank test) in disease-free survival time was observed across the four genetic risk groups (higher vs. lower risk). In the multivariable Cox proportional hazards regression analysis, the PsO-Hi and CD-Hi groups demonstrated a higher hazard ratio than the PsO-Lo and CD-Lo genetic reference group (hazard ratio 8.34, 95% confidence interval 4.17–16.7; P < 0.001). This trend was also observed in both the group with psoriasis onset first and the group with CD onset first. Conclusions These findings suggest that the development of comorbid psoriasis and CD is significantly associated with a higher genetic risk of both conditions, a trend that was consistent regardless of the disease of first onset. Future studies should validate these findings in an independent cohort.