Causal associations between inflammatory bowel disease and primary biliary cholangitis: a two-sample bidirectional...

Area of Science:

• Genetics
• Gastroenterology
• Immunology

Background:

• Hepatobiliary diseases are linked to inflammatory bowel disease (IBD).
• Previous studies suggest a causal link between IBD and primary sclerosing cholangitis (PSC).
• The causal relationship between IBD and primary biliary cholangitis (PBC) remains unclear.

Purpose of the Study:

• To investigate the potential causal association between IBD subtypes (ulcerative colitis [UC] and Crohn's disease [CD]) and primary biliary cholangitis (PBC).
• To explore the reverse causal relationship, examining if PBC influences the risk of developing UC or CD.

Main Methods:

• Utilized genome-wide association study (GWAS) statistics for PBC, UC, and CD.
• Employed two-sample Mendelian randomization (MR) analyses, including inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) methods.
• Conducted sensitivity analyses and reverse MR analysis to ensure result robustness and explore bidirectional causality.

Main Results:

• Inverse variance-weighted (IVW) analysis indicated that UC is associated with an increased risk of PBC (OR 1.35, P=0.02).
• IVW analysis also showed CD is associated with an increased risk of PBC (OR 1.18, P=0.02).
• Reverse MR analysis found no significant evidence that PBC increases the risk of UC or CD.

Conclusions:

• IBD subtypes (UC and CD) are associated with an increased incidence of PBC.
• PBC does not appear to increase the incidence of IBD subtypes.
• Recognizing IBD and PBC as potential mutual risk factors can inform clinical management strategies.