Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Eur J Cardiothorac Surg. 2024 Jun 3;65(6). doi: 10.1093/ejcts/ezae229.
The causal association between immune cell traits and aortic aneurysm remains unknown.
We performed a bidirectional two-sample Mendelian randomization analysis to explore the causality between 731 immune cell characteristics and the risk of abdominal aortic aneurysm and thoracic aortic aneurysms through publicly available genetic data, respectively. To examine heterogeneity and horizontal pleiotropy, Cochran's Q test and MR-Egger intercept were utilized. Additionally, multivariable Mendelian randomization analysis and meta-analysis were performed in further analysis.
We found that 20 immune phenotypes had a suggestive causality on abdominal aortic aneurysm, and 15 immune phenotypes had a suggestive causal effect on thoracic aortic aneurysm. After further false discovery rate adjustment (q value <0.1), CD20 on IgD+ CD38- B cell (q = 0.053) and CD127 on CD28+ CD4+ T cell (q = 0.096) were associated with an increased risk of abdominal aortic aneurysm, respectively, indicating a significant causality between them. After adjusting for smoking, there is still statistical significance between CD127 on CD28+ CD4+ T cell and abdominal aortic aneurysm. However, after adjusting for lipids, no statistical significance can be observed between CD127 on CD28+ CD4+ T cells and abdominal aortic aneurysm. Furthermore, there is still statistical significance between CD20 on IgD+ CD38- B cells and abdominal aortic aneurysm after adjusting for lipids and smoking, which was further identified by meta-analysis.
We found a causal association between immune cell traits and aortic aneurysm by genetic methods, thus providing new avenues for future mechanism studies.
免疫细胞特征与主动脉瘤之间的因果关系尚不清楚。
我们通过公开的遗传数据，分别进行了双向两样本 Mendelian 随机化分析，以探讨 731 种免疫细胞特征与腹主动脉瘤和胸主动脉瘤风险之间的因果关系。为了检验异质性和水平多效性，我们使用了 Cochran's Q 检验和 MR-Egger 截距。此外，我们还进行了多变量 Mendelian 随机化分析和荟萃分析。
我们发现 20 种免疫表型与腹主动脉瘤具有因果关系的提示，15 种免疫表型与胸主动脉瘤具有因果关系的提示。在进一步进行虚假发现率调整（q 值<0.1）后，IgD+CD38-B 细胞上的 CD20（q=0.053）和 CD28+CD4+T 细胞上的 CD127（q=0.096）与腹主动脉瘤的风险增加相关，表明它们之间存在显著的因果关系。在调整吸烟因素后，CD28+CD4+T 细胞上的 CD127 与腹主动脉瘤之间仍存在统计学意义。然而，在调整脂质后，CD28+CD4+T 细胞上的 CD127 与腹主动脉瘤之间则无统计学意义。此外，在调整脂质和吸烟因素后，IgD+CD38-B 细胞上的 CD20 与腹主动脉瘤之间仍存在统计学意义，这一结果通过荟萃分析进一步得到了验证。
我们通过遗传方法发现了免疫细胞特征与主动脉瘤之间的因果关系，从而为未来的机制研究提供了新的途径。
