Investigating the causal relationship and potential shared diagnostic genes between primary biliary cholangitis and...

Area of Science:

• Immunology
• Genetics
• Hepatology

Background:

• Observational studies suggest a link between primary biliary cholangitis (PBC) and systemic lupus erythematosus (SLE).
• The causal relationship between these two autoimmune diseases remains unclear.

Purpose of the Study:

• To investigate the bidirectional causal association between PBC and SLE using Mendelian randomization.
• To identify shared genetic biomarkers for PBC and SLE.

Main Methods:

• Bidirectional two-sample Mendelian randomization (MR) with multiple sensitivity analyses.
• Multivariable MR (MVMR) to assess confounders.
• Transcriptomic analysis (WGCNA, GO, KEGG, LASSO) and single-cell analysis to identify shared genes.

Main Results:

• MR analysis revealed a significant bidirectional causal effect between PBC and SLE.
• No confounding effects from BMI, smoking, or drinking were detected.
• Four genes (PARP9, ABCA1, CEACAM1, DDX60L) were identified as potential shared diagnostic biomarkers, highly expressed in SLE patient monocytes.

Conclusions:

• This study establishes a bidirectional causal relationship between PBC and SLE.
• Identified PARP9, ABCA1, CEACAM1, and DDX60L as potential shared diagnostic genes, offering insights into disease mechanisms.