Study on the causal relationship between metabolites and non-alcoholic fatty liver disease based on Mendelian randomization analysis
10.3969/j.issn.1673-9701.2025.12.007
- VernacularTitle:基于孟德尔随机化分析的代谢物与非酒精性脂肪性肝病的因果关系研究
- Author:
Fubo WU
1
;
Shunzhong ZHANG
;
Hongkai NIU
;
Yong WEI
Author Information
1. 滨州医学院第二临床医学院,山东烟台 264100
- Publication Type:Journal Article
- Keywords:
Non-alcoholic fatty liver disease;
Mendelian randomization;
Metabolites;
Genome-wide association study
- From:
China Modern Doctor
2025;63(12):30-35
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the causal relationship between circulating metabolites and non-alcoholic fatty liver disease(NAFLD)using Mendelian randomization analysis.Methods Summary statistics from genome-wide association study provided by Nightingale Health and the FinnGen Consortium were retrospectively collected.A two-sample Mendelian randomization analysis was performed to assess the causal effects of 233 blood metabolites on NAFLD,with the inverse-variance weighting method as the primary analytical approach.Results Elevated levels of glycoprotein acetylation(OR=3.30,95％CI:1.64-6.62,P=0.0008),the ratio of free cholesterol to total lipids in very low-density lipoprotein(VLDL)(OR=3.50,95％CI:1.63-7.48,P=0.0013),serum total triglycerides(OR=2.26,95％CI:1.38-3.70,P=0.0012),saturated fatty acids(OR=2.47,95％CI:1.40-4.36,P=0.0018),total cholesterol in VLDL(OR=2.20,95％CI:1.36-3.59,P=0.0015),the ratio of triglycerides to total lipids in very large high-density lipoprote(HDL)(OR=2.91,95％CI:1.53-5.55,P=0.0011),and triglycerides in very small VLDL(OR=2.27,95％CI:1.43-3.62,P=0.0006)were positively associated with NAFLD.Conversely,total cholesterol in high-density lipoprotein 2(OR=0.44,95％CI:0.27-0.71,P=0.0007)and total cholesterol in HDL(OR=0.44,95％CI:0.28-0.72,P=0.0009)were inversely associated with NAFLD.Heterogeneity tests indicated no significant heterogeneity among instrumental variables,confirming the robustness of the findings.Conclusion This study identified seven metabolites associated with an increased risk of NAFLD and two metabolites linked to a reduced risk,highlighting their potential roles in the pathogenesis and progression of NAFLD.
