健康状况和社会经济地位介导生殖特征对非酒精性脂肪性肝病的因果效应：孟德尔随机化研究的证据

Health condition and socioeconomic status mediate the causal effect of reproductive traits on nonalcoholic fatty liver disease: evidence from Mendelian randomization study.

作者信息

Wang Qiaoyun, Wang Liming, Hao Rui, Zhang Lijiu, Wang Wenyan, Xia Lingling

机构信息

Department of Infections Disease, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Department of Gynecology and Obstetrics, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

出版信息

Front Endocrinol (Lausanne). 2024 Aug 30;15:1419964. doi: 10.3389/fendo.2024.1419964. eCollection 2024.

DOI:10.3389/fendo.2024.1419964

PMID:39280015

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11393784/

Abstract

BACKGROUND

Observational data posits a correlation between reproductive traits and nonalcoholic fatty liver disease (NAFLD), but their causal inference is still unclear. This investigation seeks to elucidate the causal influence of reproductive traits on NAFLD and determine the intervening role of health condition and socioeconomic status in these connections.

METHODS

Utilizing a Mendelian Randomization (MR) approach, this research leveraged a comprehensive dataset from the Genome-wide Association Study (GWAS) database. The study incorporated body mass index, major depression, educational level, household income and Townsend deprivation index as intermediary variables. Initially, a bidirectional two-sample MR study was conducted to explore the genetic associations between reproductive traits and NAFLD. Then, two-step MR analyses were implemented to quantify the extent of mediation by these indicators. The weighted inverse variance method was the primary analytical approach, complemented by several sensitivity analyses to affirm the robustness of the MR assumptions. Finally, these findings were validated in the FinnGen research.

RESULTS

The bidirectional MR analysis indicated that earlier reproductive traits (age at menarche, age at first sexual intercourse, and age at first birth) were associated with an elevated risk of NAFLD, absent any evidence of the reverse relationship. Body mass index accounted for 35.64% of the association between premature menarche and NAFLD. Additionally, body mass index, major depression, educational level and household income mediated 41.65%, 14.35%, 37.88%, and 18.59% of the connection between early sexual intercourse and NAFLD, respectively. Similarly, these same variables elucidated 36.36%, 15.58%, 41.56%, and 22.73% of the correlation between younger age at first birth and NAFLD.

CONCLUSION

Our study elucidated the causal relationships between reproductive traits and NAFLD. Potential underlying mechanisms may involve factors such as body mass index, major depression, educational attainment and household income.

摘要

背景

观察性数据表明生殖特征与非酒精性脂肪性肝病（NAFLD）之间存在关联，但其因果推断仍不明确。本研究旨在阐明生殖特征对NAFLD的因果影响，并确定健康状况和社会经济地位在这些关联中的中介作用。

方法

本研究采用孟德尔随机化（MR）方法，利用来自全基因组关联研究（GWAS）数据库的综合数据集。该研究纳入了体重指数、重度抑郁症、教育水平、家庭收入和汤森贫困指数作为中介变量。首先，进行了双向两样本MR研究，以探索生殖特征与NAFLD之间的遗传关联。然后，实施了两步MR分析，以量化这些指标的中介程度。加权逆方差法是主要的分析方法，并辅以多项敏感性分析，以确认MR假设的稳健性。最后，这些发现在芬兰基因研究中得到了验证。

结果

双向MR分析表明，较早的生殖特征（初潮年龄、首次性交年龄和首次生育年龄）与NAFLD风险升高相关，没有任何反向关系的证据。体重指数占初潮过早与NAFLD之间关联的35.64%。此外，体重指数、重度抑郁症、教育水平和家庭收入分别介导了首次性交过早与NAFLD之间关联的41.65%、14.35%、37.88%和18.59%。同样，这些相同的变量分别解释了首次生育年龄较小与NAFLD之间相关性的36.36%、15.58%、41.56%和22.73%。