Association Between Inflammatory Bowel Disease and Both Psoriasis and Psoriatic Arthritis: A Bidirectional 2-Sample Mendelian Randomization Study.

Importance: Psoriasis, psoriatic arthritis, and inflammatory bowel disease, ie, Crohn disease and ulcerative colitis, are chronic systemic immune-mediated disorders affecting an increasing proportion of adults and children worldwide. Observational studies have suggested an association between inflammatory bowel disease and psoriasis and vice versa. So far, however, it remains unclear whether and in which direction causal relationships exist. Objective: To investigate the association between inflammatory bowel disease, particularly Crohn disease and ulcerative colitis, and psoriasis or psoriatic arthritis. Design, Setting, and Participants: A bidirectional 2-sample mendelian randomization study was conducted using summary statistics from genome-wide association studies including up to 463 372 European individuals. Total and direct effects were derived performing an iterative radial and robust inverse-variance weighted method within the univariable and multivariable mendelian randomization setting, respectively. Causal estimates were verified using a validation inflammatory bowel disease sample, a series of pleiotropy-robust mendelian randomization methods, and sensitivity analyses based on a PhenoScanner search in conjunction with network analysis. Data analysis was performed from April to May 2022. Main Outcomes and Measures: Inflammatory bowel disease, Crohn disease, ulcerative colitis, psoriasis, and psoriatic arthritis were used as both exposures and outcomes.
Results: The European samples included 12 882 cases of inflammatory bowel disease and 5621 cases of psoriasis. The proportion of women ranged between 48% and 56%. Genetically predicted inflammatory bowel disease was associated with higher risk of psoriasis (pooled odds ratio [OR], 1.10; 95% CI, 1.05-1.15; P < .001) and psoriatic arthritis (pooled OR, 1.10; 95% CI, 1.04-1.18; P = .003). In contrast with ulcerative colitis, the Crohn disease subentity was associated with psoriasis (OR, 1.16; 95% CI, 1.12-1.20; P < .001) and psoriatic arthritis (OR, 1.13; 95% CI, 1.06-1.20; P < .001). Regarding the reverse directions, no notable associations could be found. Conclusions and Relevance: Findings of this mendelian randomization study support a causal effect between inflammatory bowel disease and psoriasis as well as psoriatic arthritis, but not vice versa. It seems that especially Crohn disease and not ulcerative colitis is responsible for the causal effect of inflammatory bowel disease on both psoriasis outcomes. These findings have implications for the management of inflammatory bowel disease and psoriasis in clinical practice.