Causal association between uric acid levels and the risk of aortic aneurysm and aortic dissection: A two-sample Mendelian randomization study.

ABSTRACT

BACKGROUND AND AIMS: Increasing numbers of studies have sought to uncover the relationship between serum uric acid (UA) levels and the risk of aortic aneurysm (AA) or aortic dissection (AD), but the causality of the associations has not been established yet. To assess this potential relationship, we conducted a two-sample Mendelian randomization (MR) analysis. METHODS AND RESULTS: We performed two-sample Mendelian randomization (MR) analysis using independent genetic variants for UA levels from a published genome-wide association study (GWAS). Summary statistics for instrument-outcome associations from FinnGen database for AA and AD. Various sensitivity analyses were performed using different MR methods including random effects inverse variance weighting, fix effects inverse variance weighting, MR-Egger, weighted median/mode, and the contamination mixture method. Genetically predicted UA levels was associated with a higher AA risk (odds ratio (OR), 1.223; 95 % confidence interval (CI), 1.058-1.388; p = 0.017) in a simple size of 209,366 individuals. No association was found between uric acid levels and the risk of AD (OR,0.812; 95 % CI, 0.423-1.200; p = 0.293). CONCLUSION: Our study suggests a significant and robust causal association between UA levels and risk of AA but did not support such a relationship between UA levels and AD risk, which might be interpreted with caution and further confirmed. These findings support a clinically relevant causal effect of serum urate levels on the risk of AA.