Metabolic characteristics of aortic aneurysm: a two-sample Mendelian randomization study

Area of Science:

• Cardiovascular Research
• Metabolomics
• Genetics

Background:

• Plasma metabolite alterations are recognized characteristics of aortic aneurysms (AA).
• Understanding these metabolic changes is crucial for identifying risk factors and potential interventions for AA.

Purpose of the Study:

• To evaluate the causal effects of circulating metabolites and their metabolic pathways on the risk of developing AA.
• Utilized a two-sample Mendelian randomization (MR) method to establish causality.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) approach.
• Utilized metabolite data from the Canadian Longitudinal Study on Aging and AA GWAS data from the FinnGen Consortium.
• Performed rigorous instrumental variable selection and employed various MR analyses, followed by metabolic pathway enrichment analysis.

Main Results:

• Identified 77 out of 1,400 analyzed metabolites with a causal relationship to AA.
• Found negative associations with AA risk for 13-hydroxyoctadecadienoic acid (13-HODE) + 9-hydroxyoctadecadienoic acid (9-HODE) and linoleoylcholine.
• Observed positive associations with AA risk for C24 ceramide and kynurenine, and identified correlations between specific metabolic pathways (valine, leucine, isoleucine, caffeine) and AA risk.

Conclusions:

• Metabolite levels and specific metabolic pathways are causally linked to aortic aneurysm risk.
• Suggests that personalized nutrition management and metabolite monitoring could be strategies to reduce AA risk and improve long-term health outcomes.