The causal relationship between inflammatory bowel disease and primary biliary cholangitis: A bidirectional...

Area of Science:

• Gastroenterology and Hepatology
• Genetic Epidemiology

Background:

• The etiological relationship between inflammatory bowel disease (IBD) and primary biliary cholangitis (PBC) remains unclear.
• Understanding this connection is crucial for patient management and therapeutic strategies.

Purpose of the Study:

• To investigate the potential bidirectional causal relationship between IBD (including ulcerative colitis [UC] and Crohn disease [CD]) and PBC.
• To leverage genetic predisposition data for robust causal inference.

Main Methods:

• Utilized bidirectional 2-sample Mendelian randomization (MR) analysis.
• Employed genome-wide association study (GWAS) data for IBD and PBC.
• Applied inverse variance weighted, weighted median, MR-Egger, and maximum likelihood methods with sensitivity analyses for heterogeneity and pleiotropy.

Main Results:

• Genetic predisposition to IBD showed a positive association with PBC risk (OR: 1.20, P < .001).
• Crohn disease (CD) demonstrated a significant positive causal effect on PBC (OR: 1.16, P < .001).
• No significant causal relationship was detected between ulcerative colitis (UC) and PBC (OR: 0.90, P = .08).
• Reverse MR analysis indicated a causal effect of PBC on IBD risk, but not specifically on CD or UC.

Conclusions:

• A bidirectional causal association exists between IBD and PBC.
• Crohn disease may exert a positive causal influence on the development of primary biliary cholangitis.
• Ulcerative colitis does not appear to have a causal relationship with primary biliary cholangitis.