重症抑郁与短暂性脑缺血发作之间的因果关系:两样本双向孟德尔随机化  

Causality between major depression and transient ischemic attack:two-sample bidirectional Mendelian randomization

作　　者：李丽[1] 胡发权 惠振[1] LI Li;HU Fa-quan;HUI Zhen(Affiliated Nanjing Hospital of Traditional Chinese Medicine,Nanjing University of Chinese Medicine,Neurology Department,Nanjing 210000,Jiangsu China)

机构地区：[1]南京中医药大学附属南京中医院脑病科,210000 [2]安徽中医药大学中医学院

出　　处：《临床精神医学杂志》2025年第1期11-15,共5页Journal of Clinical Psychiatry

基　　金：江苏省中医药科技发展计划项目基金(MS2022043)。

摘　　要：目的:探讨重症抑郁与短暂性脑缺血发作之间的遗传因果关系。方法:选取来自IEU数据库的重症抑郁全基因组关联研究(genome-wide association studies,GWAS)汇总数据,来自FinnGen数据库的短暂性脑缺血发作GWAS汇总数据,对其采用逆方差加权(inverse-variance weighting,IVW)、MR-Egger、加权中位数、简单模式和加权模式进行孟德尔随机化分析。采用Cochrane’s Q检验检测孟德尔随机化结果的异质性,使用Egger-intercept检验多效性,用留一法、散点图分析来研究这种关联的敏感性。结果:IVW方法显示重症抑郁是短暂性脑缺血发作的独立危险因素(OR=1.29,95%CI:1.09~1.53),Egger-intercept结果为P=0.88,不具有水平多效性,Cochrane’s Q检验结果提示该研究存在一定的异质性(P<0.05)。随后采用随机效应模型,IVW具有统计学意义(P=0.03)。反向MR分析显示短暂性脑缺血发作不是重症抑郁患病风险的危险因素(P=0.404)。结论:重症抑郁症是短暂性脑缺血发作的危险因素,短暂性脑缺血发作对重症抑郁风险增加的因果关系无法明确。Objective:To explore the genetic underpinnings linking major depression and transient ischemic attack,investigating potential causal relationships and underlying mechanisms.Method:We utilized pooled genome-wide association study(GWAS)data on major depression from the IEU database and transient ischemic attack from the FinnGen database.Mendelian randomization analysis was conducted using methods including inverse-variance weighting(IVW),MR-Egger,weighted median,simple mode,and weighted mode to investigate potential causal relationships.Cochrane's Q test was employed to assess heterogeneity in the Mendelian randomization results,while the Egger-intercept test was conducted to evaluate the presence of pleiotropy.Sensitivity of the association was further examined through leave-one-out analysis and scatterplot evaluation.Results:The IVW method identified major depression as an independent risk factor for transient ischemic attack(OR=1.29,95%CI:1.09-1.53).The Egger-intercept test yielded a result of P=0.88,indicating no evidence of horizontal pleiotropy.However,Cochrane's Q test revealed some heterogeneity in the study(P<0.05).A subsequent random-effects model was applied,yielding a statistically significant result for IVW(P=0.03).Reverse Mendelian randomization analysis indicated that transient ischemic attack is not a risk factor for developing major depression(P=0.404).Conclusion:Two-sample bidirectional Mendelian randomization analysis showed that major depression is a risk factor for transient ischemic attack,but the causal relationship between transient ischemic attack and the increased risk of major depression is unclear.

关 键 词：重症抑郁 短暂性脑缺血发作 孟德尔随机化 因果关系 

分 类 号：R749.4[医药卫生—神经病学与精神病学]