Causal effects from inflammatory bowel disease on liver function and disease: a two-sample Mendelian randomization...

Area of Science:

• Gastroenterology and Hepatology
• Genetic Epidemiology
• Complex Disease Etiology

Background:

• Patients with inflammatory bowel disease (IBD) exhibit liver function abnormalities and increased susceptibility to liver diseases.
• The precise causal relationship between IBD and specific liver outcomes remains incompletely understood.

Purpose of the Study:

• To investigate the potential causal associations between ulcerative colitis (UC) and Crohn's disease (CD), two major forms of IBD, and various liver function and disease phenotypes.
• To leverage Mendelian randomization to infer causality from observational genetic data.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis utilized genome-wide association study (GWAS) data for UC, CD, liver function traits (hepatic biochemistries, liver fat, liver iron), and liver diseases (cholelithiasis, NAFLD, PSC, PBC).
• The inverse-variance weighted (IVW) method was the primary analytical approach, with GWAS of C-reactive protein (CRP) used as a positive control.

Main Results:

• Genetically predicted UC showed a causal association with decreased albumin (ALB) levels and lower liver iron content.
• Genetically predicted Crohn's disease (CD) was causally associated with increased alkaline phosphatase (ALP) levels.
• Both UC and CD were causally linked to an increased risk of primary sclerosing cholangitis (PSC), and CD was further associated with an increased risk of primary biliary cholangitis (PBC).
• No significant causal relationship was found between UC or CD and the risk of cholelithiasis or non-alcoholic fatty liver disease (NAFLD).

Conclusions:

• Ulcerative colitis (UC) causally influences albumin (ALB) levels and liver iron content.
• Crohn's disease (CD) causally affects alkaline phosphatase (ALP) levels.
• Both UC and CD are causally associated with an increased risk of primary sclerosing cholangitis (PSC), and CD specifically increases the risk of primary biliary cholangitis (PBC).