Analysis of causal relationship between immune cells and intracranial aneurysm: A mendelian randomization study

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY Journal of Neurorestoratology Pub Date : 2024-11-15 DOI:10.1016/j.jnrt.2024.100168

Yang Zhang , Sifei Wang , Yiming Huang , Miaowen Jiang , Baoying Song , Di Wu , Ming Wei , Ming Li , Xunming Ji

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Abstract

Background

Immune cells have been detected in intracranial aneurysms (IAs). However, the causal effect of immune cell phenotypes on IAs remains unclear and difficult to comprehensively analyze.

Methods

Instrumental variables for 731 immunophenotypes were extracted from publicly available genetic databases. The influence of these immune cell traits on IAs was evaluated using the Mendelian randomization (MR) method. Five MR analysis methods, with inverse-variance-weighted as the main method, along with a comprehensive sensitivity analysis, were used to determine reliability of the results. Multivariable MR analysis was performed to correct for interactions between different immune cell phenotypes.

Results

Overall, 27 immune cell traits exhibited significant causal effects on IAs. Among them, 13 immunophenotypes increased the risk of IA progression. Conversely, 14 immune cell characteristics might protect against IAs. Following false discovery rate correction, two hazardous and three protective immunophenotypes remained significant. Moreover, multivariate MR analysis showed that only naive CD4− CD8− T cells %T cells remained causally associated with a risk of IA, while CD19 on IgD+ CD38− naive B cells inhibited development of IAs.

Conclusions

Our study shows that immune cell traits and IAs are causally correlated, providing a new theoretical framework for understanding immune-IA crosstalk.

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免疫细胞与颅内动脉瘤的因果关系分析：孟德尔随机化研究

背景在颅内动脉瘤（IAs）中发现了免疫细胞。方法从公开的遗传数据库中提取了 731 种免疫表型的工具变量。采用孟德尔随机化（MR）方法评估了这些免疫细胞性状对IAs的影响。以反方差加权法为主要方法的五种 MR 分析方法以及全面的敏感性分析被用来确定结果的可靠性。进行了多变量 MR 分析，以校正不同免疫细胞表型之间的相互作用。其中，13种免疫表型增加了IA进展的风险。相反，有 14 种免疫细胞特征可预防原发性心肌梗死。经误诊率校正后，两种危险性免疫表型和三种保护性免疫表型仍具有显著性。此外，多变量 MR 分析表明，只有天真 CD4- CD8- T 细胞 %T 细胞仍与 IA 风险存在因果关系，而 IgD+ CD38- 天真 B 细胞上的 CD19 可抑制 IA 的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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