Causal relationships between human blood metabolites and intracranial aneurysm and aneurysmal subarachnoid hemorrhage: a Mendelian randomization study

Jia Jiang; Siming Gui; Dachao Wei; Xiheng Chen; Yudi Tang; Jian Lv; Wei You; Ting Chen; Shu Yang; Huijian Ge; Youxiang Li

doi:10.3389/fneur.2023.1268138

Causal relationships between human blood metabolites and intracranial aneurysm and aneurysmal subarachnoid hemorrhage: a Mendelian randomization study

Front Neurol. 2023 Dec 14:14:1268138. doi: 10.3389/fneur.2023.1268138. eCollection 2023.

Authors

Jia Jiang^#¹, Siming Gui^#¹, Dachao Wei^#¹, Xiheng Chen², Yudi Tang¹, Jian Lv¹, Wei You¹, Ting Chen³, Shu Yang¹, Huijian Ge¹, Youxiang Li¹

Affiliations

¹ Department of Neurosurgery, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
³ School of Biomedical Engineering, Capital Medical University, Beijing, China.

^# Contributed equally.

Abstract

Objective: The aim of this study was to assess the causal relationships between blood metabolites and intracranial aneurysm, aneurysmal subarachnoid hemorrhage, and unruptured intracranial aneurysm.

Methods: Our exposure sample consisted of 7,824 individuals from a genome-wide association study of human blood metabolites. Our outcome sample consisted of 79,429 individuals (7,495 cases and 71,934 controls) from the International Stroke Genetics Consortium, which conducted a genome-wide association study of intracranial aneurysm, aneurysmal subarachnoid hemorrhage, and unruptured intracranial aneurysm. We identified blood metabolites with a potential causal effect on intracranial aneurysms and conducted sensitivity analyses to validate our findings.

Results: After rigorous screening and Mendelian randomization tests, we found four, two, and three serum metabolites causally associated with intracranial aneurysm, aneurysmal subarachnoid hemorrhage, and unruptured intracranial aneurysm, respectively (all P < 0.05). Sensitivity analyses confirmed the robustness of these associations.

Conclusions: Our Mendelian randomization analysis demonstrated causal relationships between human blood metabolites and intracranial aneurysm, aneurysmal subarachnoid hemorrhage, and unruptured intracranial aneurysm. Further research is required to explore the potential of targeting these metabolites in the management of intracranial aneurysm.

Keywords: Mendelian randomization; blood metabolites; intracranial aneurysm; risk factors; single-nucleotide polymorphisms.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Beijing Natural Science Foundation (grant no. M22007), the National Natural Science Foundation of China (grant nos. 82271319 and 82171289), and the Natural Science Foundation of Hebei Province of China (grant no. F2020202053).