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Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
[Causal relationship between the triglyceride-glucose index and non-alcoholic fatty liver disease: A Mendelian
Yina Wang1, Yuanguo Chen2, Yang Wang3
1Department of Geriatrics, Second Xiangya Hospital, Central South University, Changsha 410011. wangyina@csu.edu.cn.
Objectives:
Non-alcoholic fatty liver disease (NAFLD) has become a major public health issue that seriously affects human health. This study aims to employ a two-sample Mendelian randomization (MR) approach to investigate the causal relationship between the triglyceride-glucose (TyG) index and NAFLD, aiming to explore the potential impact of the TyG index on NAFLD.
Methods:
Summary-level data for the TyG index were obtained from published genome-wide association study (GWAS) based on the UK Biobank, while GWAS summary data for NAFLD were retrieved from the IEU Open GWAS database. The inverse-variance weighted (IVW) method was used as the primary analysis, complemented by the weighted median (WM) method and the MR-Egger regression to further assess the causal relationship. Cochran's Q test was used to evaluate heterogeneity. Horizontal pleiotropy was assessed using MR-Egger regression, and the MR pleiotropy residual sum and outlier (MR-PRESSO) method was applied to detect and remove outliers. Leave-one-out analysis was conducted to assess the robustness of the results, and funnel plots were generated to evaluate reliability. Finally, MR Steiger directionality tests were performed to confirm the validity of the causal direction.
Results:
The MR-PRESSO method identified outliers (rs2081687 and rs483082), which were excluded. After removal, IVW analysis showed that the TyG index was significantly positively associated with NAFLD (OR=1.798, 95% CI 1.466 to 2.207, P=1.904E-08). Consistent results were observed using the WM method (OR=1.621, 95% CI 1.144 to 2.296, P=0.007) and the MR-Egger method (OR=1.630, 95% CI 1.153 to 2.304, P=0.006). No significant heterogeneity or horizontal pleiotropy was detected. Leave-one-out analysis showed that no single nucleotide polymorphism (SNP) had a substantial influence on the results. Funnel plots were generally symmetrical, supporting the robustness and reliability of the findings. MR Steiger directionality tests did not detect any evidence of reverse causality.
Conclusions:
This MR study suggests a causal relationship between the TyG index and NAFLD. Elevated TyG index levels are associated with an increased risk of NAFLD, with no evidence supporting reverse causation. These findings provide a reference for identifying potential risk factors for NAFLD and developing effective prevention strategies.