基于孟德尔随机化法的抗抑郁药与心肌梗死因果关联研究
Causal association study of antidepressants and myocardial infarction based on Mendelian randomization method
李梓铭 1余克富 2史卫忠 2赵志刚 2杨莉3
作者信息
- 1. 首都医科大学 药学院,北京 100069;首都医科大学附属北京天坛医院 药学部,北京 100070
- 2. 首都医科大学附属北京天坛医院 药学部,北京 100070
- 3. 首都医科大学 药学院,北京 100069
- 折叠
摘要
目的 探讨抗抑郁药与心肌梗死的因果关联研究.方法 采用双样本孟德尔随机化(MR)方法,应用芬兰数据库和MRC Integrative Epidemiology Unit数据库中GWAS数据,选取与抗抑郁药相关的遗传变异作为工具变量,通过逆方差加权法分析抗抑郁药与心肌梗死的因果关系,并采用异质性检验、水平多效性及留一法等敏感性分析评估结果的稳健性.结果 共筛选16个与抗抑郁药相关的遗传变异作为工具变量,抗抑郁药与心肌梗死之间存在因果关联(OR=1.160,95%CI:1.058～1.272,P<0.05),异质性检验结果显示,抗抑郁药与心肌梗死的因果关联不存在异质性(P>0.05);水平多效性检验结果显示,遗传代理的抗抑郁药对心肌梗死不存在水平多效性的影响(P>0.05).结论 抗抑郁药可能增加患者心肌梗死风险,临床用药应密切观察.
Abstract
Objective To investigate the causal relationship between antidepressants and myocardial infarction.Methods A two-sample Mendelian randomization(MR)method was used,utilizing GWAS data from the Finnish database and the MRC Integrative Epidemiology Unit database.Genetic variants related to antidepressants were selected as instrumental variables,and the causal relationship between antidepressants and myocardial infarction was analyzed using the inverse vari-ance weighted method.Sensitivity analyses were conducted to assess the robustness of the results including heterogeneity tests,horizontal pleiotropy tests,and leave-one-out analysis.Results A total of 16 genetic variants associated with antidepressants were selected as instrumental variables.There was a causal relationship between antidepressants and myocardial infarction(OR=1.160,95%CI:1.058 to 1.272,P<0.05).The heterogeneity test results indicated no heterogeneity in the causal rela-tionship between antidepressants and myocardial infarction(P>0.05).The horizontal pleiotropy test results showed no hori-zontal pleiotropic effects of the genetic proxies for antidepressants on myocardial infarction(P>0.05).Conclusion Antidepres-sants may increase the risk of myocardial infarction in patients,and clinical use should be closely monitored.
关键词
孟德尔随机化/抗抑郁药/心肌梗死/心血管疾病/冠心病Key words
Mendelian randomization/antidepressant/myocardial infarction/cardiovascular disease/coronary heart disease引用本文复制引用
基金项目
首都医科大学科研培育基金(PYZ23117)
出版年
2024
NETL
NSTL
万方数据