Causality of inflammatory bowel disease and seborrheic keratosis: A bidirectional two-sample Mendelian randomization study

Background: Previous studies have revealed a potential link between inflammatory bowel disease (IBD) and seborrheic keratosis (SK). However, whether this association is causal or confounded remains unknown. Methods: We conducted this two-sample Mendelian randomization (TSMR) analysis to clarify bidirectional causality between IBD, including its two primary conditions Crohn's disease (CD) and ulcerative colitis (UC), and SK. The summary genetic data of IBD, CD, UC and SK were obtained from accessible genome-wide association studies (GWAS). This TSMR study was primarily performed using inverse-variance weighted (IVW) method, complemented by MR-Egger, weighted median (WM), Bayesian weighted MR (BWMR), MR-robust adjusted profile score (MR-RAPS), MR-pleiotropy residual sum and outlier (MR-PRESSO), and radial IVW MR analyses with modified second-order weights (IVW [Mod 2nd]) methods. Assessment of sensitivity and identification of potential outliers were subsequently conducted to aid interpretation of results. Results: The forward MR results showed that IBD [odds ratio (OR) = 1.068, 95% confidence interval (CI) = 1.010-1.129, p = 0.020) and its subtype CD (OR = 1.088, 95%CI = 1.038-1.139, p < 0.001) increased the risk of SK. However, the occurrence of SK could not be affected by UC (OR = 1.090, 95%CI = 0.977-1.216, p = 0.123). In the reverse analysis, no causal relationship between SK and IBD (OR = 0.905, 95%CI = 0.813-1.008, p = 0.069), UC (OR = 0.959, 95%CI = 0.860-1.068, p = 0.443), and CD (OR = 0.933, 95%CI = 0.846-1.029, p = 0.165) was identified. Conclusion: These findings demonstrate that IBD and its subtype CD could increase the incidence of SK in European populations, whereas SK does not affect IBD occurrence.