Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Curr Neurovasc Res. 2023;20(2):270-279. doi: 10.2174/1567202620666230703122140.
Autoimmune diseases are associated with cardiovascular and cerebrovascular diseases. However, whether myasthenia gravis (MG) and ischemic stroke (IS) are causally related remains unclear.
This study aimed to evaluate potential causal links between MG and IS using bidirectional Mendelian randomization (MR).
We conducted a two-sample MR analysis to assess the potential associations between MG and IS. Genetic variants associated with MG and IS as well as their subtypes were extracted from genome-wide association studies by meta-analysis. The inverse-variance weighted method was used for the main MR analysis. Sensitivity analyses, including the MREgger, simple mode, simple median, weighted mode, and weighted median approaches were applied to test the robustness of the results.
The MR analyses indicated no causal effects of general MG on IS of all causes (odds ratio [OR] = 0.990, 95% confidence interval [CI]: 0.953-1.029, = 0.615), large vessel atherosclerosis stroke (OR = 0.943, 95% CI: 0.856-1.039, = 0.233), cardioembolic stroke (OR = 0.975, 95% CI: 0.867-1.096, = 0.670), and small vessel occlusion stroke (OR = 1.059, 95% CI 0.974-1.150, = 0.178). Subgroup analyses indicated no causal effects of early- or late-onset MG on IS and its subtypes (all > 0.05). The reverse MR analysis showed no significant causal associations of IS on MG (all > 0.05).
Bidirectional MR analysis did not provide evidence to support a causal relationship between genetically predicted MG and IS, although observational studies have found such a potential link.
自身免疫性疾病与心血管和脑血管疾病相关。然而，重症肌无力（MG）和缺血性中风（IS）是否存在因果关系尚不清楚。
本研究旨在使用双向孟德尔随机化（MR）评估 MG 和 IS 之间潜在的因果关系。
我们进行了两样本 MR 分析，以评估 MG 和 IS 之间的潜在关联。通过荟萃分析从全基因组关联研究中提取与 MG 和 IS 及其亚型相关的遗传变异。主要 MR 分析采用逆方差加权法。采用 MREgger、简单模式、简单中位数、加权模式和加权中位数方法进行敏感性分析，以检验结果的稳健性。
MR 分析表明，一般 MG 与所有病因的 IS（比值比 [OR] = 0.990，95%置信区间 [CI]：0.953-1.029， = 0.615）、大动脉粥样硬化性中风（OR = 0.943，95%CI：0.856-1.039， = 0.233）、心源性栓塞性中风（OR = 0.975，95%CI：0.867-1.096， = 0.670）和小血管闭塞性中风（OR = 1.059，95%CI 0.974-1.150， = 0.178）无因果关系。亚组分析表明，早发性或晚发性 MG 与 IS 及其亚型（均 ＞ 0.05）之间无因果关系。反向 MR 分析表明，IS 对 MG 无显著因果关系（均 ＞ 0.05）。
双向 MR 分析未提供证据支持遗传预测的 MG 与 IS 之间存在因果关系，尽管观察性研究发现了这种潜在联系。
