Causal Relationships Between Human Blood Metabolites and Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: a Mendelian Randomization Study

ObjectiveThe aim of this study was to assess the causal relationships between blood metabolites and intracranial aneurysm, aneurysmal subarachnoid hemorrhage, and unruptured intracranial aneurysm.MethodsOur exposure sample consisted of 7,824 individuals from a genome-wide association study of human blood metabolites. Our outcome sample consisted of 79,429 individuals (7,495 cases and 71,934 controls) from the International Stroke Genetics Consortium, which conducted a genome-wide association study of intracranial aneurysm, aneurysmal subarachnoid hemorrhage, and unruptured intracranial aneurysm. We identified blood metabolites with a potential causal effect on intracranial aneurysms and conducted sensitivity analyses to validate our findings.ResultsAfter rigorous screening and Mendelian randomization tests, we found four, two, and three serum metabolites causally associated with intracranial aneurysm, aneurysmal subarachnoid hemorrhage, and unruptured intracranial aneurysm, respectively (all P < 0.05). Sensitivity analyses confirmed the robustness of these associations.ConclusionsOur Mendelian randomization analysis demonstrated causal relationships between human blood metabolites and intracranial aneurysm, aneurysmal subarachnoid hemorrhage, and unruptured intracranial aneurysm. Further research is required to explore the potential of targeting these metabolites in the management of intracranial aneurysm.