基于孟德尔随机化探索广泛的血管周围间隙负荷与缺血性卒中及其亚型和短暂性脑缺血发作的因果关系  

Exploring the causal relationship between extensive perivascular space burden and ischemic stroke and its subtypes and transient ischemic attack based on Mendelian randomization

作　　者：褚学红 申英杰 王耀楼 董晓 刘圆圆 冯艳 姜缪文 李明 吉训明[1] 吴川杰[1] Chu Xuehong;Shen Yingjie;Wang Yaolou;Dong Xiao;Liu Yuanyuan;Feng Yan;Jiang Miaowen;Li Ming;Ji Xunming;Wu Chuanjie(Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Department of Neurosurgery,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China;Department of Neurology,Suzhou Hospital of Anhui Medical University,Suzhou 234000,Anhui Province,China;Beijing Institute for Brain Disorders,Capital Medical University,Beijing 100069,China;Beijing Institute of Geriatrics,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院神经内科,北京100053 [2]哈尔滨医科大学附属第一医院神经外科,哈尔滨150001 [3]安徽医科大学附属宿州医院神经内科,安徽宿州234000 [4]首都医科大学北京脑重大疾病研究院,北京100069 [5]首都医科大学宣武医院北京老年医学研究所,北京100053

出　　处：《首都医科大学学报》2025年第1期22-33,共12页Journal of Capital Medical University

基　　金：国家自然科学基金项目(82071468、82271507);北京市杰出青年科学基金项目(JQ24041);北京市医师科学家培训项目(BJPSTP-2024-04)。

摘　　要：目的探究广泛的血管周围间隙(extensive perivascular space,EPVS)负荷与缺血性卒中(ischemic stroke,IS)(包括其亚型)和短暂性脑缺血发作(transient ischemic attack,TIA)之间是否存在遗传因果关系。方法利用来自大规模全基因组关联研究的汇总数据,通过孟德尔随机化(Mendelian randomization,MR)分析,研究不同部位的EPVS与IS及其亚型和TIA之间的关联。采用多种MR方法评估EPVS负荷与IS及其亚型和TIA之间的因果关系。应用多变量MR以减轻潜在的混杂因素,并进行敏感性分析以增强结果的稳健性。随后,利用Meta分析整合来自不同来源的、不同部位EPVS负荷与IS之间因果关系的数据。此外,采用反向MR观察各种IS类型对EPVS的影响。最后,进行连锁不平衡评分回归,以评估暴露和结果之间的遗传相关性。结果脑白质(OR=1.12,95%CI:1.01~1.25;P=0.04)和基底节(OR=1.57,95%CI:1.30~1.89;P<0.01)中的EPVS负荷均是IS的显著危险因素。基底节中的EPVS负荷也是小动脉闭塞型IS的危险因素(OR=4.56;95%CI:2.57~8.27;P=5.95×10^(-7))。此外,IS和TIA后,基底节EPVS负荷似乎也存在潜在的增加。结论广泛的白质和基底节血管周围间隙负荷可能是预测IS的重要指标。Objective To investigate the association between extensive perivascular space(EPVS)burden in different locations and ischemic stroke(IS),its subtypes,and transient ischemic attack(TIA)through Mendelian randomization(MR)analysis.Methods The summary data from large-scale Genome-wide Association Studies(GWAS)and various MR methods were employed.We applied multivariable MR to mitigate potential confounding factors and conduct sensitivity analyses to enhance result robustness.Subsequently,meta-analysis was utilized to integrate causal relationships between EPVS burden in different locations and IS from various sources.Additionally,reverse MR was employed to observe the impact of various IS types on EPVS burden.Finally,linkage disequilibrium score regression was conducted to assess genetic correlations between exposures and outcomes.Results EPVS burden in both the white matter(OR=1.12,95%CI:1.01-1.25;P=0.04)and basal ganglia(OR=1.57,95%CI:1.30-1.89;P<0.01)are significant risk factors for IS.EPVS burden in the basal ganglia is also a risk for IS(small-vessel)(OR=4.56,95%CI:2.57-8.27;P=5.95×10^(-7)).After IS and TIA there seems to be a potential increase in extensive basal ganglia perivascular space burden.Conclusions Extensive white matter perivascular space burden and extensive basal ganglia perivascular space burden may serve as important indicators to predict IS.

关 键 词：广泛的血管周围间隙负荷 缺血性卒中 因果关系 孟德尔随机化 

分 类 号：R743.33[医药卫生—神经病学与精神病学]