Causal links between inflammatory bowel disease and both psoriasis and psoriatic arthritis: a bidirectional two-sample Mendelian randomization study

IntroductionPsoriasis (PsO), psoriatic arthritis (PsA) and inflammatory bowel disease (IBD), i.e. Crohn’s disease (CD) and ulcerative colitis (UC) are chronic systemic immune-mediated disorders affecting an increasing proportion of adults and children worldwide. Observational studies suggested an association between IBD and PsO and vice versa. However, so far it remains unclear whether a causal relationship exists.MethodsTo investigate the causal paths, a bidirectional two-sample Mendelian randomization (MR) study was conducted using summary statistics from genome-wide association studies (GWASs) including up to 463,372 Europeans. Total and direct effects were derived performing an iterative radial and robust inverse-variance weighted method within the univariable and multivariable MR setting, respectively. Causal estimates were verified using a validation IBD-sample, a series of pleiotropy-robust MR-methods, and sensitivity analyses based on PhenoScanner search in conjunction with network analysis.ResultsGenetically predicted IBD was associated with higher risk of PsO (pooled OR=1.10; 95% CI: (1.05; 1.15); P=1⋅10−4) and PsA (pooled OR=1.10; 95% CI: (1.04; 1.18); P=3⋅10−3). In contrast to UC, the CD subentity was related to PsO (OR=1.16; 95% CI: (1.12; 1.20); P=1⋅10−14) and PsA (OR=1.13; 95% CI: (1.06; 1.20); P=1⋅10−4). Regarding the reverse directions, no notable associations could be found.ConclusionsThis study supports a causal effect between IBD and PsO as well as PsA, but not vice versa. It seems that mainly CD and not UC is responsible for the causal impact of IBD on both psoriasis outcomes. These findings have implications for the management of IBD and psoriasis in clinical practice.