AUTHOR=Shu Yufeng , Yang Bocheng , Liu Xuanyou , Xu Meihua , Deng Chao , Wu Hao 

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

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1320842

DOI=10.3389/fmed.2023.1320842

ISSN=2296-858X

ABSTRACT=Background: Accumulating evidence has shown that patients with inflammatory bowel disease (IBD) have liver function abnormalities and are susceptible to liver diseases. However, the existence of a causal relationship between IBD and liver function or disease remains unclear.
Methods: A two-sample Mendelian randomization (MR) analysis was performed using genetic associations from publicly available genome-wide association studies (GWAS). These associations encompassed ulcerative colitis (UC), Crohn’s disease (CD), liver function traits, and liver disease phenotypes. The liver function traits comprised hepatic biochemistries, percent liver fat, and liver iron content from UK Biobank. Furthermore, the liver disease phenotypes included cholelithiasis, non-alcoholic fatty liver disease (NAFLD), primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC) in cohorts of European ancestry. The primary estimation used the inverse-variance weighted method, with GWAS of C-reactive protein (CRP) in UK Biobank serving as a positive control outcome.
Results: Genetically predicted UC is causally associated with decreased levels of albumin (ALB) and liver iron content, while genetically predicted CD is causally associated with increased levels of alkaline phosphatase (ALP). Moreover, genetically predicted UC or CD increases the risk of PSC, and CD increases the risk of PBC. Neither UC nor CD causally increases the risk of cholelithiasis and NAFLD.
Conclusion: UC affects the levels of ALB and liver iron content, while CD affects the levels of ALP. Both UC and CD increase the risk of PSC, and CD increases the risk of PBC.