Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study
Chencheng Ma, Weiwei Zhang, Lei Mao, Guangjian Zhang, Yuqi Shen, Hanxiao Chang, Xiupeng Xu, Zheng Li, Lu Hua
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.