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

Introduction: alterations in plasma metabolites are increasingly recognized as an important characteristic of aortic aneurysms (AA). Objective: to evaluate the causal effects of circulating metabolites and their metabolic pathways on the risk of developing AA using a two-sample Mendelian randomization (MR) method. Methods: metabolite data were derived from the Canadian Longitudinal Study on Aging, and the genome-wide association study (GWAS) summary data on AA were obtained from the FinnGen Consortium. Instrumental variables were rigorously selected, and a range of MR analysis methods were employed to identify metabolites associated with AA, followed by metabolic pathway enrichment analysis of these metabolites. Results: among the 1,400 metabolites analyzed, 77 were found to demonstrate a causal relationship to AA. Notably, 13-hydroxyoctadecadienoic acid (13-HODE) + 9-hydroxyoctadecadienoic acid (9-HODE) (OR = 0.835, p = 0.001) and linoleoylcholine (OR = 0.867, p = 0.012) were negatively associated with AA risk, while C24 ceramide (d18:1/24:0) (OR = 1.167, p = 0.002) and kynurenine (OR = 1.096, p = 0.021) were positively associated. The synthesis pathways for valine, leucine, and isoleucine were positively correlated with AA, whereas the caffeine metabolic pathway showed a negative correlation. Conclusion: personalized nutrition management combined with metabolite level monitoring may contribute to reducing the risk of AA and improve long-term health outcomes in affected individuals.