Frontiers in Neurology (Sep 2022)

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

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

DOI
https://doi.org/10.3389/fneur.2022.948989
Journal volume & issue
Vol. 13

Abstract

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ObjectiveTo investigate the link between genetic variants associated with plasma homocysteine levels and risk of intracranial aneurysm (IA) using two-sample Mendelian randomization.MethodsWe 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.ResultsThe 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.ConclusionUsing gene-related instrumental variables, the Mendelian randomization analyses demonstrated a lack of an association between plasma homocysteine levels and IAs or aneurysmal subarachnoid hemorrhage.

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