基于两样本孟德尔随机化探讨脂蛋白(a)和脑小血管病的因果关系  

Study on the causal relationship between lipoprotein(a)and cerebrovascular disease by two-sample Mendelian randomization analysis

作　　者：刘雪情 宫秀群 刚玉文 项心怡 李晗晓 陆军[2] LIU Xue-qing;GONG Xiu-qun;GANG Yu-wen;XIANG Xin-yi;LI Han-xiao;LU Jun(Department of Neurology,the First Affiliated Hospital of Anhui University of Technology,Huainan,Anhui 232001,China;不详)

机构地区：[1]安徽理工大学第一附属医院神经内科,安徽淮南232001 [2]安徽理工大学医学院,安徽淮南232001

出　　处：《现代预防医学》2024年第9期1562-1567,共6页Modern Preventive Medicine

基　　金：2021年安徽省高校自然科学研究重点项目(KJ2021A0434)。

摘　　要：目的利用孟德尔随机化方法(Mendelian randomization,MR)来探究脂蛋白(a)[Lipoprotein(a),Lp(a)]与脑小血管病(cerebral small vascular disease,CSVD)之间的因果关系。方法采用两个大样本的全基因组关联公共数据库,根据遗传位点满足相互独立,挑选出和Lp(a)相关联的单核苷酸多态性位点(P<5×10^(-8))作为工具变量。本研究的主要结局为脑白质高信号(white matter hyperintensity,WMH)、脑微出血以及腔隙性梗塞。使用逆方差加权法(inverse variance weighting,IVW)评估Lp(a)与CSVD的因果关系,通过MR-Egger和MR-PRESSO进行敏感性分析,评估工具变量的多效性。进一步采用加权中位数法、简单中位数法、最大似然比法等分析方法检验结果是否可靠。结果IVW结果表明Lp(a)与WMH之间存在正向风险关系(OR=1.083,95%CI:1.035~1.134,P<0.001),但Lp(a)与脑微出血(P=0.568)和腔隙性梗塞(P=0.651)没有相关性。MR-Egger分析表明有关Lp(a)和WMH的MR分析结果不受水平多效性的影响(P=0.721)。结论MR分析显示Lp(a)与WMH发生风险升高有关。Objective To explore the causal relationship between lipoprotein(a)[Lp(a)]and cerebral small vascular disease(CSVD)by Mendelian randomization(MR)analysis.Methods Using genome-wide association study(GWAS)public database,the single nucleotide polymorphisms independently associated with Lp(a)(P<5×10^(-8))were selected as instrumental variables(IVs).The main outcomes of this study were white matter hyperintensity(WMH),cerebral microhemorrhage,and lacunar infarction.Inverse variance weighted(IVW)mothod was used to evaluate the causal relationship between Lp(a)and CSVD.Sensitivity analysis was carried out by MR-Egger and MR-PRESSO to evaluate the pleiotropy of IVs.Furthermore,weighted median method,simple median method,and maximum likelihood ratio method were used to test the reliability of the results.Results IVW results showed that there was a positive risk relationship between Lp(a)and WMH(OR=1.083,95%CI:1.035-1.134,P<0.001),but Lp(a)was not correlated with cerebral microhemorrhage(P=0.568)and lacunar infarction(P=0.651).MR-Egger analysis showed that the MR analysis of Lp(a)and WMH was not affected by horizontal pleiotropy(P=0.721).Conclusion MR analysis shows that Lp(a)is related to the increased risk of WMH.

关 键 词：脑白质高信号 脂蛋白(a) 孟德尔随机化 工具变量 因果关系 

分 类 号：R743[医药卫生—神经病学与精神病学]