焦虑症与心血管疾病风险关联的双向孟德尔随机化研究  

Bidirectional Mendelian Randomization of the Association Between Anxiety Disorders and Cardiovascular Disease Risk

作　　者：朱文娟 徐瑞宁 杨颖 智宏 王莉娜[1] Zhu Wenjuan;Xu Ruining;Yang Ying(Department of Epidemiology and Biostatistics,School of Public Health,Southeast University,Nanjing 210009,China)

机构地区：[1]东南大学公共卫生学院流行病与卫生统计学系,南京210009 [2]东南大学附属中大医院心血管内科,南京210009

出　　处：《华中科技大学学报(医学版)》2025年第2期217-222,227,共7页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81673259);江苏省研究生科研与实践创新计划项目(No.SJCX23_0095)。

摘　　要：目的采用双向两样本孟德尔随机化方法研究焦虑症和冠心病、房颤、心力衰竭、卒中和心肌梗死等心血管疾病的因果关联及方向。方法研究数据均来自全基因组关联研究汇总数据集,纳入丹麦灵北基金会综合精神病学研究iPSYCH队列提供的焦虑症全基因组关联研究数据以及其他5个心血管疾病相关数据库。采用逆方差加权法(IVW)汇总关联效应指标,MR-Egger回归、加权中位数法、加权模式和简单模式四种方法补充验证,同时进行异质性、水平多效性和逐个剔除检验等敏感性分析。结果逆方差加权法和MR-Egger回归方法分析结果均提示焦虑症会增加冠心病发病风险(IVW:OR=1.0001,95%CI=1.0001~1.0025,P=0.040;MR-Egger:OR=1.0030,95%CI=1.0009~1.0058,P=0.013),且尚未发现存在反向因果关联。本研究的工具变量不存在水平多效性与异质性。敏感性分析提示结果较稳健。结论焦虑症和冠心病发病风险增加存在因果关联,但尚未发现与房颤、心力衰竭、卒中和心肌梗死等其他心血管疾病风险增加有关,同时未见反向因果关联效应。Objective To investigate the causal relationships between anxiety disorders and coronary heart disease(CHD),atrial fibrillation(AF),heart failure(HF),stroke and myocardial infarction(MI)risks by using the bidirectional two-sample Mendelian randomization study method.Methods The data were collected from the genome-wide association study(GWAS)conducted within the population-based Danish Lundbeck Foundation Initiative for Integrative Psychiatric Research(iPSYCH)study,as well as from five other databases related to cardiovascular diseases.The inverse variance weighting(IVW)method was used to produce the main results,and four methods,including MR-Egger regression,weighted median method,weighted model,and simple model,supplemented the results.Sensitivity analyses such as heterogeneity,horizontal pleiotropy,and leave-one-out analysis were also performed.Results The IVW and MR-Egger regression showed that anxiety disorders would increase the risk of coronary heart disease(IVW:OR=1.0001,95%CI=1.0001—1.0025,P=0.040;MR-Egger:OR=1.0030,95%CI=1.0009—1.0058,P=0.013).There was no evidence of a causal effect of cardiovascular diseases on anxiety disorders risks.There was no horizontal pleiotropy and heterogeneity in the instrumental variables of this study.The result of sensitivity analysis was robust.Conclusion The study supports the causal effect of anxiety disorders on CHD risk,but no association is found with an increased risk of other cardiovascular diseases,such as AF,HF,stroke,and MI.No reverse causal association effect is observed.

关 键 词：焦虑症 心血管疾病 孟德尔随机化 因果推断 

分 类 号：R541.4[医药卫生—心血管疾病] R749.7[医药卫生—内科学]