孟德尔随机化
医学
置信区间
邦费罗尼校正
冲程(发动机)
优势比
内科学
观察研究
遗传关联
全基因组关联研究
心脏病学
单核苷酸多态性
遗传学
基因型
生物
统计
遗传变异
工程类
基因
机械工程
数学
作者
Renjie Liu,Xiaorui Shi,Jianghua Feng,Jianmin Piao,Zhuo Yang,Yuhao Zhao,Haoyuan Yin,Xuan Chen
标识
DOI:10.1007/s40120-023-00500-w
摘要
Recent observational studies have reported the association between ischemic stroke (IS) and cerebral microbleeds (CMBs). Whether this reflects a causal association remains to be established. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) analysis to comprehensively evaluate the causal association of IS and CMBs.The summary-level genome-wide association studies (GWASs) data of IS were obtained from the GIGASTROKE consortium (62,100 European ancestry cases and 1,234,808 European ancestry controls). All IS cases could be further divided into large-vessel atherosclerosis stroke (LVS, n = 6399), cardio-embolic stroke (CES, n = 10,804) and small-vessel occlusion stroke (SVS, n = 6811). Meanwhile, we used publicly available summary statistics from published GWASs of CMBs (3556 of the 25,862 European participants across 2 large initiatives). A bidirectional MR analysis was conducted using inverse-variance weighting (IVW) as the major outcome, whereas MR-Egger and weighted median (WM) were used to complement the IVW estimates as they can provide more robust estimates in a broader set of scenarios but are less efficient (wider CIs). A Bonferroni-corrected threshold of p < 0.0125 was considered significant, and p values between 0.0125 and 0.05 were considered suggestive of evidence for a potential association.We detected that higher risk of IS [IVW odds ratio (OR) 1.47, 95% confidence interval (CI) 1.04-2.07, p = 0.03] and SVS (IVW OR 1.62, 95% CI 1.07-2.47, p = 0.02) were significantly associated with CMBs. Reverse MR analyses found no significant evidence for a causal effect of CMBs on IS and its subtypes.Our study provides potential evidence that IS and SVS are causally linked to increased risk of CMBs. Further research is needed to determine the mechanisms of association between IS and CMBs.
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