Volume 24 Issue 4
Apr.  2026
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Article Navigation >  Chinese Journal of General Practice  > 2026  >  24(4): 682-686
LIANG Xiyao, ZENG Xin, DAI Yan, CHEN Jiaxing, FENG Yitian, LIU Yuan. Bidirectional two-sample Mendelian randomization investigation of the causal association between liver function indicators and autoimmune liver diseases[J]. Chinese Journal of General Practice, 2026, 24(4): 682-686. doi: 10.16766/j.cnki.issn.1674-4152.004468
Citation: LIANG Xiyao, ZENG Xin, DAI Yan, CHEN Jiaxing, FENG Yitian, LIU Yuan. Bidirectional two-sample Mendelian randomization investigation of the causal association between liver function indicators and autoimmune liver diseases[J]. Chinese Journal of General Practice, 2026, 24(4): 682-686. doi: 10.16766/j.cnki.issn.1674-4152.004468
shu

Bidirectional two-sample Mendelian randomization investigation of the causal association between liver function indicators and autoimmune liver diseases

doi: 10.16766/j.cnki.issn.1674-4152.004468
  • 1.

    Department of Infectious Diseases, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China

Funds:

 81603092

  • Received Date: 2025-10-08
    Abstract
  •   Objective  To investigate the causal associations between liver function indices and autoimmune liver diseases (AILD) using a bidirectional two-sample Mendelian randomization (MR) approach.  Methods  Genome-wide association study (GWAS) data for liver function indices and AILD were obtained from the open GWAS database. Forward MR analysis was performed with 9 liver function indices including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT): as exposures, while 3 types of AILD autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) were considered as outcomes. Reverse MR analysis was subsequently conducted to validate potential causal effects in the opposite direction. The inverse variance weighted (IVW) method was used as the primary analytical approach. Sensitivity analyses, including weighted median, MR-Egger, MR-PRESSO, horizontal pleiotropy test, and heterogeneity test were conducted to verify result robustness.  Results  Forward MR analysis showed that ALT (OR=1.719, 95% CI: 1.276-2.316, P < 0.001), AST (OR=1.358, 95% CI: 1.012-1.824, P=0.041), and GGT (OR=1.535, 95% CI: 1.255-1.877, P < 0.001) were positively associated with AIH. ALP and GGT exhibited positive causal relationships with PBC (ALP: OR=1.309, P < 0.001; GGT: OR=1.168, P=0.007) and PSC (ALP: OR=1.208, P=0.037; GGT: OR=1.155, P=0.046). Reverse MR analysis revealed causal associations between AIH and GGT (OR=1.004, P=0.021), PBC/PSC and ALP (PBC: OR=1.007, P=0.018; PSC: OR=1.008, P=0.039), as well as PBC/PSC and GGT (PBC: OR=1.014, P=0.003; PSC: OR=1.010, P < 0.001).  Conclusion  At the genetically predicted level, elevated ALT, AST, and GGT are associated with an increased risk of AIH, and AIH may, in turn, influence GGT levels. Bidirectional causal relationships were identified between ALP/GGT and PBC/PSC. These findings provide novel insights into the non-invasive diagnosis and potential therapeutic strategies for AILD.

     

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