Mendelian randomization demonstrates a causal link between peripheral circulating acylcarnitines and intracranial...

Area of Science:

• Cardiovascular Science
• Metabolomics
• Genetics

Background:

• Intracranial aneurysms (IAs) are a leading cause of subarachnoid hemorrhage (SAH), characterized by vascular remodeling.
• The precise triggers for IA development and rupture remain unclear.
• Abnormalities in circulating proteins and metabolites have been observed in IA patients.

Purpose of the Study:

• To investigate the potential causal relationship between peripheral circulating metabolites and proteins and intracranial aneurysms (IAs).
• To explore the mediating role of hypertension in the association between specific metabolites and IAs.

Main Methods:

• Utilized two-sample Mendelian randomization (MR) analysis.
• Analyzed data from the FinnGen study and published GWAS datasets.
• Included 191 blood metabolites and 1398 proteins in the analysis.

Main Results:

• Identified palmitoylcarnitine, stearoylcarnitine, and 2-tetradecenoylcarnitine as causal contributors to IAs and their ruptures.
• Two-step mediation MR analysis indicated that hypertension mediates the causal link between these metabolites and IAs.

Conclusions:

• Blood metabolites palmitoylcarnitine, stearoylcarnitine, and 2-tetradecenoylcarnitine are causally associated with IA formation and rupture.
• Hypertension plays a partial mediating role in this causal pathway.