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 -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 > 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.
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| http://dx.doi.org/10.3389/fneur.2022.948989 | DOI Listing |
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