Genetic Link Between Primary Biliary Cholangitis and Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study

Background: Although observational studies have shown that primary biliary cholangitis (PBC) and rheumatoid arthritis (RA) frequently coincide, it is unclear whether a causative relationship exists between the two diseases. This study aimed to assess the causal associations between PBC and RA. Methods We performed a two-sample Mendelian randomization (MR) analysis. Following a strict assessment, genome-wide association study datasets were used to select potential candidate single-nucleotide polymorphisms. Sensitivity analyses were performed to determine whether the MR results were affected by heterogeneity and pleiotropy. Results We found that genetically increased PBC risk had a positive causal effect on RA (inverse-variance weighted odds ratio [IVW OR] 1.149, 95% confidence interval [CI] 1.063–1.241, P  < 0.001). Horizontal pleiotropy was unlikely to influence causation according to the MR-Egger regression (intercept=-0.028, P  = 0.263). Sensitivity analyses using the leave-one-out method further confirmed that the MR analysis results were reliable and robust. In contrast, the reverse MR analysis found no evidence of a causal effect of RA on PBC (IVW OR 1.132, 95% CI 0.881–1.454, P  = 0.333). Conclusions Our findings provide evidence that PBC has a unidirectional effect on RA in the European population. Given the increased risk of PBC in RA and both being autoimmune conditions, awareness and thorough screening are imperative in clinical practice.