-
- Academic Editor
-
-
-
†These authors contributed equally.
Background: Identifying effective pharmacological
interventions to prevent the progressive enlargement and rupture of aortic
aneurysms (AAs) is critical. Previous studies have suggested links between
metformin use and a decreased incidence of AAs. In this study, we employed
Mendelian randomization (MR) to investigate causal effects of metformin’s targets
on AA risk and to explore the underlying mechanisms underlying these effects.
Methods: To examine the relationship between metformin use and AA risk,
we implemented both two-sample MR and multivariable MR analyses. Utilizing
genetic instrumental variables, we retrieved cis-expression quantitative trait
loci (cis-eQTL) data for potential targets of metformin from the Expression
Quantitative Trait Loci Genetics Consortium (eQTLGen)
Consortium and Genotype-Tissue Expression (GTEx) project. Colocalization analysis was employed to ascertain
the probability of shared causal genetic variants between single nucleotide
polymorphisms (SNPs) associated with eQTLs and AA. Results: Our findings
reveal that metformin use reduces AA risk, exhibiting a protective effect with an
odds ratio (OR) of 4.88