The causal relationship between inflammatory bowel disease and primary biliary cholangitis: A bidirectional two-sample Mendelian randomization study

The cause-and-effect relationship between inflammatory bowel disease (IBD) and primary biliary cholangitis (PBC) has not been fully elucidated. Thus, this study explored their causal relationship through bidirectional 2-sample Mendelian randomization (MR). Genome-wide association studies were used to obtain data. Single-nucleotide polymorphisms (SNPs) closely related to IBD (including ulcerative colitis [UC] and Crohn disease [CD]) and PBC were screened, and the methods used included inverse variance weighted and the weighted median method. MR analysis was performed using maximum likelihood and MR-Egger. Sensitivity analysis was performed to identify heterogeneity and horizontal pleiotropy, thereby assessing the reliability of the results. Gene-predicted IBD (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.09-1.31; P < .001) and CD (OR: 1.16, 95% CI: 1.08-1.25; P < .001) were positively associated with PBC. However, we failed to detect statistical evidence of correlation between UC and PBC (OR: 0.90, 95% CI: 0.80-1.01, P = .08). Reverse analysis demonstrated a causal relationship between genetic predisposition to PBC and increased risk of IBD, but no reverse causation for CD and UC. This MR study elucidates a bidirectional association between IBD and PBC. Specifically, CD exerted a potential positive causal effect on PBC, while no reverse causation was observed. Conversely, UC exhibited no causal relationship with PBC.