Immune mechanisms play a crucial role in the development of stroke. However, immune-related phenotypes are diverse and their associations with stroke are largely unknown. Here, we aimed to systematically explore the causal role of immune cell traits in stroke and its subtypes by leveraging data from genome-wide association studies (GWASs). Exposure data were obtained from a recent GWAS on 731 immune cell traits profiled by flow cytometry involving 3757 individuals. By conducting two-sample univariable Mendelian randomization (MR) analyses, each immune cell trait was assessed for causal relationships with stroke outcomes from the MEGASTROKE Consortium (40,585 cases and 406,111 controls). The robustness of the MR results was verified by a series of sensitivity analyses. We identified three significant associations after Bonferroni correction ( < 1.37E-05). Increased CD27 expression on memory B cell (OR = 1.23, 95% CI = 1.14-1.33, = 2.78E-08), IgDCD38dim B cell (OR = 1.16, 95% CI = 1.09-1.23, = 5.98E-06) and unswitched memory B cell (OR = 1.18, 95% CI = 1.10-1.27, = 1.09E-05) were associated with a higher risk of large-artery atherosclerotic stroke (LAS). Furthermore, expression quantitative trait loci data also indicated elevated blood CD27 mRNA level was a risk factor for LAS (OR = 1.37, 95% CI = 1.02-1.84, = 0.037). This study provided genetic evidence of the causal relationship between immune cell traits and stroke, highlighting the role of CD27 on memory B cell as a novel factor for LAS risk.

中文翻译：

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免疫细胞特征在中风中的因果作用：孟德尔随机化研究

免疫机制在中风的发展中起着至关重要的作用。然而，免疫相关表型多种多样，其与中风的关系在很大程度上尚不清楚。在这里，我们的目标是利用全基因组关联研究（GWAS）的数据，系统地探讨免疫细胞特征在中风及其亚型中的因果作用。暴露数据来自最近的 GWAS，通过流式细胞术分析了涉及 3757 名个体的 731 种免疫细胞特征。通过进行两个样本单变量孟德尔随机化 (MR) 分析，评估了每个免疫细胞特征与 MEGASTROKE 联盟（40,585 例病例和 406,111 例对照）中风结果的因果关系。MR 结果的稳健性通过一系列敏感性分析得到验证。经过 Bonferroni 校正后，我们发现了三个显着关联 (< 1.37E-05)。记忆 B 细胞（OR = 1.23，95% CI = 1.14-1.33，= 2.78E-08）、IgDCD38dim B 细胞（OR = 1.16，95% CI = 1.09-1.23，= 5.98E-06）和未转换的记忆 B 细胞（OR = 1.18，95% CI = 1.10-1.27，= 1.09E-05）与大动脉粥样硬化性卒中 (LAS) 的较高风险相关。此外，表达数量性状位点数据还表明血液 CD27 mRNA 水平升高是 LAS 的危险因素（OR = 1.37，95% CI = 1.02-1.84，= 0.037）。这项研究提供了免疫细胞特征与中风之间因果关系的遗传证据，强调了 CD27 对记忆 B 细胞作为 LAS 风险新因素的作用。