Causal relationship between circulating immune cells, cytokines and different types of autoimmune liver diseases: A univariable and multivariable Mendelian randomization study

Autoimmune liver diseases (AILDs) are a group of liver diseases characterized by immune dysfunction. Recent studies have proposed a potential correlation among immune cells, cytokines, and AILDs. However, the causal nature of this relationship remains to be elucidated. Summary-level Genome-Wide Association Studies (GWAS) statistical data for primary biliary cholangitis and primary sclerosing cholangitis were obtained from FinnGen, while autoimmune hepatitis and immune trait statistics were sourced from the GWAS Catalog. GWAS data for 41 inflammatory cytokines were acquired from the University of Bristol. The inverse-variance weighted method was the primary Mendelian randomization (MR) analysis method, with sensitivity and inverse MR analyses performed to assess result stability. Under the premise of satisfying the MR hypothesis, our analysis supported the existence of potential causal relationships between different immunophenotypes, cytokines, and AILDs. 10 immune cell phenotypes and 7 cytokines with potential causal relationships with AILDs were identified. For different types of AILDs, 4 immune phenotypes and 4 cytokines were found to be associated with primary biliary cholangitis, 4 immune phenotypes and 2 immune factors were associated with primary sclerosing cholangitis, and 3 immune phenotypes and 1 cytokine were associated with autoimmune hepatitis. However, we did not find any evidence of reverse causality between immunophenotypes, cytokines, and AILDs. MR analysis found a potential causal relationship between several immune phenotypes, cytokines, and AILDs, suggesting differences in immune responses across various types of AILDs.