Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

Chencheng Ma; Weiwei Zhang; Lei Mao; Guangjian Zhang; Yuqi Shen; Hanxiao Chang; Xiupeng Xu; Zheng Li; Hua Lu

doi:10.3389/fneur.2022.948989

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

Front Neurol. 2022 Sep 28:13:948989. doi: 10.3389/fneur.2022.948989. eCollection 2022.

Authors

Chencheng Ma^{1

2}, Weiwei Zhang³, Lei Mao^{1

2}, Guangjian Zhang^{1

2}, Yuqi Shen^{1

2}, Hanxiao Chang^{1

2}, Xiupeng Xu^{1

2}, Zheng Li^{1

2}, Hua Lu^{1

2}

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Neurosurgery, Jiangsu Province Hospital, Nanjing, China.
³ Department of Ophthalmology, Third Medical Center of Chinese PLA General Hospital, Nanjing, China.

Abstract

Objective: To investigate the link between genetic variants associated with plasma homocysteine levels and risk of intracranial aneurysm (IA) using two-sample Mendelian randomization.

Methods: We used single-nucleotide polymorphisms associated with human plasma homocysteine levels as instrumental variables for the primary analysis in a genome-wide association study of 44,147 subjects of European ancestry. Summary-level statistics were obtained for 79,429 individuals, including 7,495 IA cases and 71,934 controls. To enhance validity, five different Mendelian randomization methods (MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) were used for the analyses.

Results: The inverse variance weighted analysis method produced P-values of 0.398 for aneurysmal subarachnoid hemorrhage [odds ratio (OR): 1.104; 95% confidence interval (CI): 0.878-1.387], 0.246 for IA (OR: 1.124; 95% CI: 0.923-1.368), and 0.644 for unruptured IA (OR: 1.126; 95% CI: 0.682-1.858). The MR-Egger analysis showed no association between IAs and homocysteine, with all P > 0.05.

Conclusion: Using gene-related instrumental variables, the Mendelian randomization analyses demonstrated a lack of an association between plasma homocysteine levels and IAs or aneurysmal subarachnoid hemorrhage.

Keywords: Mendelian randomization; causality; cerebrovascular disease; hyperhomocysteinemia; intracranial aneurysm.