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

Area of Science:

• Immunology
• Genetics
• Epidemiology

Background:

• Systemic lupus erythematosus (SLE) and primary biliary cholangitis (PBC) are autoimmune diseases with recognized associations.
• The causal relationship between SLE and PBC remains unclear.

Purpose of the Study:

• To investigate the bidirectional causation between SLE and PBC using Mendelian randomization (MR) analysis.

Main Methods:

• Acquired summary data from Genome-wide association studies (GWAS) for SLE and PBC.
• Employed inverse variance weighted (IVW) method as the primary analysis.
• Conducted sensitivity analyses, meta-analysis, and multivariable MR to assess robustness and confounding factors.

Main Results:

• Univariable MR analysis provided strong evidence for a causal effect of SLE on PBC (OR=1.17, P<0.001).
• Reverse MR analysis indicated a causal effect of PBC on SLE (OR=1.39, P<0.001).
• Sensitivity analyses confirmed the absence of horizontal pleiotropy and heterogeneity, with causality remaining significant after adjusting for confounders.

Conclusions:

• This study provides statistical evidence supporting a potential bidirectional causal relationship between SLE and PBC.
• Further research is warranted to elucidate the underlying biological mechanisms connecting these two conditions.