基于孟德尔随机化探讨第一胎胎儿出生体重与胎儿未来非酒精性脂肪性肝病风险之间的关联  

Relationship between first-born weight and future risk of nonalcoholic fatty liver disease based on Mendelian randomization

作　　者：王车 卫朗秋 张博晖 张瑜娇 邹佳盈 徐守竹 刘启玲 史传道 WANG Che;WEI Langqiu;ZHANG Bohui;ZHANG Yujiao;ZOU Jiaying;XU Shouzhu;LIU Qiling;SHI Chuandao(School of Public Health,Shaanxi University of Chinese Medicine,Shaanxi Province,Xianyang 712046,China)

机构地区：[1]陕西中医药大学公共卫生学院,陕西咸阳712046

出　　处：《中国医药导报》2025年第4期139-144,共6页China Medical Herald

基　　金：陕西省自然科学基础研究计划项目(2024JC-YBMS-729)。

摘　　要：目的探讨第一胎胎儿出生体重与胎儿未来非酒精性脂肪性肝病(NAFLD)风险之间的因果关联,旨在为两者之间的潜在关联提供更可靠的依据。方法基于IEU Open GWAS数据库,筛选出相互独立且与第一胎胎儿的出生体重强相关的工具变量。采用逆方差加权法、MR-Egger回归法、加权模式法、简单模式法和加权中位数法分别评估第一胎胎儿出生体重和NAFLD的因果效应,采用Cochran’s Q检验、MR-Egger截距法、留一法分析工具变量的异质性及敏感性,漏斗图进行偏倚性分析。结果正向分析显示,逆方差加权法中第一胎胎儿出生体重与NAFLD发病存在因果关联(OR=0.530,95%CI:0.343~0.819,P=0.004)。单核苷酸多态性(SNP)间不存在异质性,不存在水平多效性;无单个SNP对结果造成显著影响。漏斗图显示工具变量对称分布。反向分析显示,第一胎胎儿出生体重和NAFLD发病不存在因果关联。结论第一胎胎儿较低的出生体重降低其未来NAFLD的患病风险,且未发现反向因果关联。Objective To investigate the causal relationship between first-born weight and future risk of nonalcoholic fatty liver disease(NAFLD),in order to provide a more reliable basis for the potential association between the two.Methods Based on IEU Open GWAS database,independent instrumental variables that were strongly correlated with the first-born weight were screened.Inverse variance weighted method,MR-Egger regression method,weighted mode method,simple median method,and weighted median method were used to respectively evaluate the causal effects of the first-born weight and NAFLD.Cochran’s Q test,MR-Egger intercept method,and leave-one-out method were used to analyze the heterogeneity and sensitivity of tool variables,and funnel plots were used for bias analysis.Results Forward analysis showed that the first-born weight in inverse variance weighted method was causally relationship with the incidence of NAFLD(OR=0.530,95%CI:0.343-0.819,P=0.004).There was no heterogeneity or horizontal pleiotropy among single nucleotide polymorphism(SNP),no single SNP had a significant impact on the results.The funnel plot showed that the instrumental variables were distributed symmetrically.Reverse analysis showed no causal relationship between first-born weight and future risk of NAFLD.Conclusion Lower first-born weight reduces the risk of future NAFLD,and no reverse causal relationship was found.

关 键 词：第一胎胎儿出生体重 非酒精性脂肪肝 因果关系 孟德尔随机化 

分 类 号：R575.5[医药卫生—消化系统]