Article Link
Collect
Submit Manuscript
Show Outline
Outline
Abstract
Keywords
Electronic Supplementary Material
References
Show full outline
Hide outline
Short Communication | Open Access

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

Yang Zhanga,b,1Sifei Wangc,1Yiming Huanga,b,1Miaowen JiangdBaoying Songa,bDi WubMing Weic,d()Ming Lib()Xunming Jib,d,e()
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
China–America Institute of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300000, China
Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

1 These authors contributed equally to this work.

Show Author Information

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.

Electronic Supplementary Material

Download File(s)
jnrt-13-1-100168_ESM.zip (5.7 MB)

References

1

Zhang Y, Cheng SJ, He Y, et al. Activated platelet-homing nanoplatform for targeting magnetic resonance imaging of aneurysm-related Thrombus in rabbits. ACS Appl Mater Interfaces. 2021;13(43):50705–50715. https://doi.org/10.1021/acsami.1c13539.

2

Arumadi A, Hrishi AP, Prathapadas U, et al. Evaluation of markers of cerebral oxygenation and metabolism in patients undergoing clipping of cerebral aneurysm under total intravenous anesthesia versus inhalational anesthesia: a prospective randomized trial (COM-IVIN trial). Brain Circ. 2023;9(4):251–257. https://doi.org/10.4103/bc.bc_66_23.

3

Bakker MK, van der Spek RAA, van Rheenen W, et al. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet. 2020;52(12):1303–1313. https://doi.org/10.1038/s41588-020-00725-7.

4

Xia JX, Peng F, Chen XG, et al. Statins may decrease aneurysm wall enhancement of unruptured fusiform intracranial aneurysms: a high-resolution 3T MRI study. Transl Stroke Res. 2024;15(6):1133–1141. https://doi.org/10.1007/s12975-023-01190-0.

5

Peng F, Xia J, Niu H, et al. Systemic immune-inflammation index is associated with aneurysmal wall enhancement in unruptured intracranial fusiform aneurysms. Front Immunol. 2023;14:1106459. https://doi.org/10.3389/fimmu.2023.1106459.

6

Martinez AN, Tortelote GG, Pascale CL, et al. Single-cell transcriptome analysis of the circle of Willis in a mouse cerebral aneurysm model. Stroke. 2022;53(8):2647–2657. https://doi.org/10.1161/STROKEAHA.122.038776.

7

Smith GD, Ebrahim S. 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32(1):1–22. https://doi.org/10.1093/ije/dyg070.

8

Du BS, Zhang ZY, Zhang H, et al. Identification and validation of core genes associated with intracranial aneurysms through bioinformatics analysis and Mendelian randomization. Brain Res. 2024;1838:149009. https://doi.org/10.1016/j.brainres.2024.149009.

9

Yu YH, Tong S, Liu T, et al. Exploring the causal role of immune cells in cerebral aneurysm through single-cell transcriptomics and Mendelian randomization analysis. Clin Exp Immunol. 2024;217(2):195–203. https://doi.org/10.1093/cei/uxae042.

10
Frösen J, Piippo A, Paetau A, et al. Growth factor receptor expression and remodeling of saccular cerebral artery aneurysm walls: implications for biological therapy preventing rupture. Neurosurgery. 2006;58(3):534–541. https://doi.org/10.1227/01.NEU.0000197332.55054.C8. ;discussion 534–541.
11

Zhang HF, Liang GB, Zhao MG, et al. Patients with intracranial aneurysms presented defects in regulatory T cells, which were associated with impairment in Tim-3 upregulation. Int Immunopharm. 2018;64:350–355. https://doi.org/10.1016/j.intimp.2018.09.020.

12

Wang W, Li H, Zhao Z, et al. The pathogenesis shared between abdominal aortic aneurysms and intracranial aneurysms: a microarray analysis. Neurosurg Rev. 2018;41(2):667–674. https://doi.org/10.1007/s10143-017-0912-2.

13

Dmitrieva OS, Shilovskiy IP, Khaitov MR, et al. Interleukins 1 and 6 as main mediators of inflammation and cancer. Biochem Mosc. 2016;81(2):80–90. https://doi.org/10.1134/S0006297916020024.

14

Xu YF, Guo P, Wang GP, et al. Integrated analysis of single-cell sequencing and machine learning identifies a signature based on monocyte/macrophage hub genes to analyze the intracranial aneurysm associated immune microenvironment. Front Immunol. 2024;15:1397475. https://doi.org/10.3389/fimmu.2024.1397475.

15

Ji H, Han YJ, Jie DY, et al. Decoding the biology and clinical implication of neutrophils in intracranial aneurysm. Ann Clin Transl Neurol. 2024;11(4):958–972. https://doi.org/10.1002/acn3.52014.

Journal of Neurorestoratology
Cite this article:
Zhang Y, Wang S, Huang Y, et al. Analysis of causal relationship between immune cells and intracranial aneurysm: A mendelian randomization study. Journal of Neurorestoratology, 2025, 13(1). https://doi.org/10.1016/j.jnrt.2024.100168
Metrics & Citations  
Article History
Copyright
Rights and Permissions
Return