Causal associations between systemic lupus erythematosus and primary biliary cholangitis: A bidirectional Mendelian randomization study.

Objectives: The association between systemic lupus erythematosus (SLE) and primary biliary cholangitis (PBC) has been increasingly recognized. However, the existence of causal connections between SLE and PBC has yet to be established. In this study, we aimed to investigate the bidirectional causation between SLE and PBC utilizing Mendelian randomization (MR) analysis. Methods: We acquired summary data from Genome-wide association studies (GWAS) for SLE and PBC from the IEU Open GWAS and FinnGen database. The inverse variance weighted (IVW) was employed as the key method to ascertain the causality between SLE and PBC. Subsequently, a range of sensitivity analyses were applied. We also performed a fixed-effects model meta-analysis to combine the MR results from different databases. Moreover, multivariable MR were conducted to clarify the roles of potential confounding factors. Results: Our univariable MR investigation provided compelling evidence supporting a causal relationship between SLE and PBC in both directions. Specifically, the IVW method demonstrated a strong casual effect of SLE on PBC (odds ratio (OR) = 1.17, 95 % confidence interval (CI) = 1.09-1.25, p < 0.001). In addition, the results of reverse MR analysis revealed that genetically predicted PBC was associated with an increased risk of SLE (OR = 1.39, 95 % CI = 1.32-1.45, p < 0.001). The sensitivity analyses indicated the absence of horizontal pleiotropy and heterogeneity. Furthermore, the causality between SLE and PBC remained significant even after adjusting for common risk factors in the multivariable MR analysis. Conclusions: Our study provides statistical evidence of a potential causal relationship between SLE and PBC, but further research is needed to the explore of the underlying mechanisms of these disorders.