Zhang Xiao, Hu Xinzhi, Fang Shiyuan, Li Jiayao, Liu Zhichao, Xie Weidun, Xu Ran, Dmytriw Adam A, Yang Kun, Ma Yan, Jiao Liqun, Wang Tao
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.
Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Neurol Ther. 2024 Jun;13(3):727-737. doi: 10.1007/s40120-024-00601-0. Epub 2024 Apr 15.
Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR).
Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method.
Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99-1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97-1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95-1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91-1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy.
This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.
既往研究报道了循环血管内皮生长因子（VEGF）与缺血性卒中（IS）之间存在有争议的关系。本研究旨在利用孟德尔随机化（MR）方法证明VEGF与IS之间的因果关系。
从公共数据库下载了两项大规模全基因组关联研究（GWAS）的汇总统计数据，其中一项研究涉及16112例测量了VEGF水平的患者，另一项研究涉及40585例IS患者，并纳入本研究。采用已发表的计算器进行MR功效计算。主要结局为任何缺血性卒中，次要结局为大动脉卒中、心源性栓塞性卒中和小血管卒中。我们采用逆方差加权（IVW）方法进行主要分析，并辅以MR-Egger回归和加权中位数方法。
纳入9个单核苷酸多态性（SNP）来代表血清VEGF水平。IVW方法显示VEGF与任何缺血性卒中（比值比[OR]为1.01，95%置信区间[CI]为0.99-1.04，p = 0.39）、心源性栓塞性卒中（OR为1.04，95%CI为0.97-1.12，p = 0.28）、大动脉卒中（OR为1.02，95%CI为0.95-1.09，p = 0.62）及小血管卒中（OR为0.98，95%CI为0.91-1.04，p = 0.46）之间均无强因果关联。这些发现在敏感性分析中仍然稳健。MR-Egger回归提示无水平多效性。
这项孟德尔随机化研究发现，遗传易感性血清VEGF水平与IS及其亚型的风险之间无关联。
