Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
Transl Stroke Res. 2022 Aug;13(4):528-532. doi: 10.1007/s12975-021-00974-6. Epub 2022 Jan 11.
We aimed to assess the potential causal association between Parkinson's disease (PD) and ischemic stroke (IS) with Mendelian randomization methods. Summary statistics data from two large-scale genome-wide association studies (GWAS) for 33,674 PD cases and 40,585 IS cases were used in this study. We used inverse variance-weighted method for primary analysis, and four other Mendelian randomization methods (weighted median, MR-Egger regression methods, robust adjusted profile score, radial regression) to test whether PD was causal for IS and its subtypes. Analyses were bidirectional to assess reverse causality. Primary analysis showed PD had a significantly causal association with IS (OR 1.04; 95% CI, 1.02-1.07; p = 0.0019), and two subtypes of IS, cardioembolic stroke (OR 1.11; 95% CI, 1.06-1.18; p = 0.0001) and large artery stroke (OR 1.08; 95% CI, 1.01-1.15; p = 0.034), but not with small-vessel stroke (p = 0.180). The point estimates from sensitivity analyses were in the same direction. There was no strong evidence for a reverse causal association between PD and IS. Using multiple Mendelian randomization methods based on large-scale GWAS, PD is a potential cause of cardioembolic stroke and large artery stroke, but not small-vessel stroke. Ischemic stroke does not cause PD.
我们旨在使用孟德尔随机化方法评估帕金森病（PD）和缺血性中风（IS）之间潜在的因果关联。本研究使用了两项针对 33674 例 PD 病例和 40585 例 IS 病例的大型全基因组关联研究（GWAS）的汇总统计数据。我们使用逆方差加权法进行主要分析，并使用另外四种孟德尔随机化方法（加权中位数、MR-Egger 回归方法、稳健调整轮廓评分、径向回归）来检验 PD 是否是 IS 及其亚型的因果因素。分析是双向的，以评估反向因果关系。主要分析表明，PD 与 IS 之间存在显著的因果关系（OR 1.04；95%CI，1.02-1.07；p=0.0019），以及 IS 的两种亚型，心源性脑栓塞（OR 1.11；95%CI，1.06-1.18；p=0.0001）和大动脉性中风（OR 1.08；95%CI，1.01-1.15；p=0.034），但与小血管性中风无关（p=0.180）。敏感性分析的点估计结果方向相同。PD 与 IS 之间没有强烈的反向因果关系的证据。使用基于大规模 GWAS 的多种孟德尔随机化方法，PD 是心源性脑栓塞和大动脉性中风的潜在原因，但不是小血管性中风的原因。缺血性中风不会导致 PD。
