【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。更多还原

【Abstract】 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.更多还原