甘油三酯-葡萄糖指数与非酒精性脂肪性肝病因果关系的孟德尔随机化研究

王轶娜; 陈元国; 王鸯; 陈露; 尹美龙; 肖晓; 黄晶; 邝晶洁; 李亚勇

doi:10.11817/j.issn.1672-7347.2025.250010

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甘油三酯-葡萄糖指数与非酒精性脂肪性肝病因果关系的孟德尔随机化研究

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甘油三酯-葡萄糖指数与非酒精性脂肪性肝病因果关系的孟德尔随机化研究
Causal relationship between the triglyceride-glucose index and non-alcoholic fatty liver disease: A Mendelian randomization study
中南大学学报(医学版) 中南大学学报(医学版) 2026年51卷第2期页码：179-188
作者机构：

1.中南大学湘雅二医院老年医学科，长沙 410011
2.中南大学湘雅三医院急诊医学科，长沙 410013
3.海南医科大学附属海南医院，海南省人民医院老年医学中心(医疗保健中心)，海口 571199
4.中国人民解放军联勤保障部队第九二一医院干部病房，长沙 410003
作者简介：

王轶娜，Email: wangyina@csu.edu.cn, ORCID: 0000-0002-0402-1795
李亚勇，副主任医师，Email: liyy999@csu.edu.cn, ORCID: 0000-0001-7092-0302
基金信息：

湖南省自然科学基金(2023JJ30786┫。This work was supported by the Natural Science Foundation of Hunan Province;China ┣2023JJ30786)
DOI：10.11817/j.issn.1672-7347.2025.250010
中图分类号：
CSTR：
收稿：2025-01-14，

纸质出版：2026-02-28
稿件说明：

王轶娜, 陈元国, 王鸯, 陈露, 尹美龙, 肖晓, 黄晶, 邝晶洁, 李亚勇. 甘油三酯-葡萄糖指数与非酒精性脂肪性肝病因果关系的孟德尔随机化研究[J]. 中南大学学报(医学版), 2026, 51(2): 179-188.

WANG Yina, CHEN Yuanguo, WANG Yang, CHEN Lu, YIN Meilong, XIAO Xiao, HUANG Jing, KUANG Jingjie, LI Yayong. Causal relationship between the triglyceride-glucose index and non-alcoholic fatty liver disease: A Mendelian randomization study[J]. Journal of Central South University. Medical Science, 2026, 51(2): 179-188.
王轶娜, 陈元国, 王鸯, 陈露, 尹美龙, 肖晓, 黄晶, 邝晶洁, 李亚勇. 甘油三酯-葡萄糖指数与非酒精性脂肪性肝病因果关系的孟德尔随机化研究[J]. 中南大学学报(医学版), 2026, 51(2): 179-188. DOI：10.11817/j.issn.1672-7347.2025.250010.

WANG Yina, CHEN Yuanguo, WANG Yang, CHEN Lu, YIN Meilong, XIAO Xiao, HUANG Jing, KUANG Jingjie, LI Yayong. Causal relationship between the triglyceride-glucose index and non-alcoholic fatty liver disease: A Mendelian randomization study[J]. Journal of Central South University. Medical Science, 2026, 51(2): 179-188. DOI：10.11817/j.issn.1672-7347.2025.250010.

摘要

目的

非酒精性脂肪性肝病(non-alcoholic fatty liver disease，NAFLD)已成为严重影响人类健康的重要公共卫生问题。本研究采用双样本孟德尔随机化(Mendelian randomization，MR)法，分析甘油三酯-葡萄糖(triglyceride-glucose，TyG)指数与NAFLD之间的因果关系，旨在探索TyG指数对NAFLD的潜在影响。

方法

TyG指数的全基因组关联分析(genome-wide association study，GWAS)汇总数据来源于基于UK Biobank的已发表研究，NAFLD的GWAS汇总数据来源于IEU Open GWAS数据库。使用逆方差加权(inverse-variance weighted，IVW)法作为主要分析方法，并辅以加权中位数(weighted median，WM)法和MR-Egger法，以进一步探讨TyG指数与NAFLD之间的因果关系。采用Cochran’s

检验评估数据异质性；通过MR-Egger法检验水平多效性，并应用MR多效性残差和与异质性检验(MR pleiotropy residual sum and outlier，MR-PRESSO)法进行离群值检验及异常数据剔除。此外，采用留一法验证结果的稳健性，绘制漏斗图评估结果的可靠性。最后，应用MR Steiger方向性检验，确保因果关系的合理性。

结果

MR-PRESSO法检测到离群值(rs2081687；rs483082)，予以剔除后，IVW法分析结果显示TyG指数与NAFLD呈显著正相关(

=1.798，95%

1.466~2.207，

=1.904E-08)，WM法(

=1.621，95%

1.144~2.296，

=0.007)和MR-Egger法(

=1.630，95%

1.153~2.304，

=0.006)显示的因果关系与IVW法一致。相关方法未检测到异质性和水平多效性，留一法亦未检测到对结果影响大的单核苷酸多态性(single nucleotide polymorphism，SNP)，漏斗图基本对称，支持结果的稳健性和可靠性。MR Steiger方向性检验未发现反向因果的SNP。

结论

TyG指数与NAFLD之间存在因果关系，TyG指数升高可增加NAFLD的发生风险，且没有证据证明二者存在反向关联，该结论可为探究NAFLD的潜在风险因素及制订有效预防策略提供参考。

Abstract

Objective

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

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 (

=1.798

95%

1.466 to 2.207

=1.904E-08). Consistent results were observed using the WM method (

=1.621

95%

1.144 to 2.296

=0.007) and the MR-Egger method (

=1.630

95%

1.153 to 2.304

=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.

Conclusion

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.

关键词

Keywords

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