Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

Area of Science:

• Genetics
• Neurology
• Cardiovascular Science

Background:

• Elevated plasma homocysteine levels are a potential risk factor for various cardiovascular diseases.
• Intracranial aneurysms (IA) are serious vascular conditions affecting the brain.
• The association between homocysteine and IA risk remains unclear.

Purpose of the Study:

• To investigate the causal relationship between genetically determined plasma homocysteine levels and the risk of intracranial aneurysm (IA).
• To assess the association between homocysteine and both ruptured and unruptured IA, as well as aneurysmal subarachnoid hemorrhage.

Main Methods:

• Two-sample Mendelian randomization analysis was employed using genetic variants (single-nucleotide polymorphisms) associated with plasma homocysteine levels.
• Genome-wide association study summary statistics from a large cohort (44,147 subjects, European ancestry) were utilized.
• Five distinct Mendelian randomization methods (MR-Egger, weighted median, inverse variance weighted, simple mode, weighted mode) were applied to ensure robust findings.

Main Results:

• Mendelian randomization analyses, including inverse variance weighted and MR-Egger methods, showed no statistically significant association between genetically predicted plasma homocysteine levels and the risk of IA.
• No significant association was observed for aneurysmal subarachnoid hemorrhage or unruptured IA.
• All tested P-values exceeded the conventional threshold for statistical significance (P > 0.05).

Conclusions:

• The study provides evidence against a causal role of plasma homocysteine levels in the pathogenesis of intracranial aneurysms.
• Genetically influenced homocysteine levels do not appear to be a significant risk factor for IA or aneurysmal subarachnoid hemorrhage.