初潮年龄与心力衰竭:一项遗传相关性与孟德尔随机化研究  

Associations between age at menarche and risk of heart failure:a genetic correlation and mendelian randomization study

作　　者：李鑫茜 盖巧玥 张璐[1] 刘振谧[1] 于川[1] 肖成汉[1] LI Xin-xi;GE Qiao-yue;ZHANG Lu;LIU Zhen-mi;YU Chuan;XIAO Cheng-han(West China School of Public Health/West China Fourth Hospital,Sichuan University,Chengdu,Sichuan610041,China)

机构地区：[1]四川大学华西公共卫生学院/四川大学华西第四医院,四川成都610041

出　　处：《现代预防医学》2023年第20期3719-3723,3784,共6页Modern Preventive Medicine

基　　金：中央高校基本科研业务费专项资金(2022SCU12021)。

摘　　要：目的采用遗传关联性分析和孟德尔随机化(MR)探究初潮年龄和心力衰竭风险的相关性和因果关联。方法基于初潮年龄(AAM)和心力衰竭(HF)的全基因组数据,采用连锁不平衡回归(LDSC)和基因组结构方程模型(Genomic SEM)评估遗传相关性,分别采用单变量MR和多变量MR探索初潮年龄对心衰风险的总效应和直接效应。结果LDSC回归分析显示AAM与HF为遗传负相关(rg=-0.271,P=1.94×10-9)。Genomic SEM分析显示调整了混杂因素后AAM与HF之间的负向偏相关。单变量MR结果显示遗传预测AAM与HF风险呈负向因果关联(IVW:OR=0.884;95%CI:0.854~0.916,P<0.001),多变量MR结果显示调整了混杂因素后负向因果关联仍然存在。结论本研究表明遗传预测的初潮年龄越早心力衰竭的风险越大。Objective To investigate the correlation and causation between age at menarche(AAM)and risk of heart failure(HF)with genetic correlation analysis and Mendelian randomization(MR).Methods Based on genome-wide association study(GWAS)data on age at menarche and heart failure,genetic correlation was assessed using linkage disequilibrium regression(LDSC)and Genomic structural equation models(Genomic SEM).Univariate MR and multivariate MR were used to explore the total and direct effects of age at menarche on heart failure risk respectively.Results There was a negative genetic correlation between AAM and HF(rg=-0.271,P=1.94×10-9).After additionally adjusting for confounders,genomic SEM analysis revealed a negative partial correlation between AAM and HF.Univariable MR results showed that genetically predicated AAM and HF risk had a negative causal effect(IVW:OR=0.884;95%CI:0.854-0.916,P<0.001),and multivariable MR results showed that the negative causal association remained after adjusting for confounders.Conclusion This study suggests that genetically predicted early age at menarche increases the risk of heart failure.

关 键 词：孟德尔随机化 初潮年龄 心力衰竭 

分 类 号：R173[医药卫生—妇幼卫生保健]