Inflammatory Bowel Disease and Rosacea: A Two-Sample Mendelian Randomization Study

Background. Inflammatory bowel disease (IBD) might increase the risk of rosacea; however, the relationship between IBD and rosacea is not determined. In this study, Mendelian randomization (MR) design was used to explore the potential causal association between IBD and rosacea. Methods. A two-sample MR was explored from large-scale genetic summary data from genome-wide association study (GWAS), including IBD (n = 59959) and its main subtype Crohn's disease (CD) (n = 40266) and ulcerative colitis (UC) (n = 45975). Summarized data of rosacea (n = 1877) were obtained from different GWAS studies. Based on previous observational studies, our main analyses were conducted by the inverse-variance weighted (IVW) method with the random-effects model, with a complementary with the other two analyses: weighted median method and MR-Egger approach. Results. The results of IVW methods demonstrated that genetically predicted IBD was significantly associated with rosacea (odds ratio (OR), 1.18 (95% CI, 1.05-1.32), P=0.004). The weighted median method and MR-Egger regression also demonstrated directionally similar results (all P < 0.05). In addition, both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between IBD and rosacea. CD was strongly associated with it in its subtype analysis (odds ratio (OR), 1.11 (95% CI, 1.01-1.22), P=0.04), and UC was also causally associated with rosacea, but its statistical significance did not appear to be significant (odds ratio (OR), 1.16 (95% CI, 0.99-1.36), P=0.07). Conclusions. Our study provided potential evidence between genetically predicted IBD and rosacea, and the degree of association of different subtypes of IBD for rosacea is different. In addition, we found that the mechanism of IBD affecting the pathogenesis of rosacea is closely related to the variation of IL23R. Blocking the IL-23 signaling pathway might be a reasonable strategy to treat IBD and prevent rosacea. Understanding the specific relationship between IBD and rosacea provides the possibility to treat both clinically and guide the development of new drugs.