Association of cardiovascular disease and urate levels with aortic aneurysm: a bilateral mendelian randomization study

Abstract

The aim of this study is to investigate the potential causal relationships between coronary artery disease (CAD), myocardial infarction (MI), urate levels, and aortic aneurysm (AA), abdominal aortic aneurysm (AAA), thoracic aortic aneurysm(TAA), aortic dissection (AD) in individuals of European ancestry. To examine the potential causal relationships between CAD, MI, and urate levels with AA, AAA, TAA, AD, respectively, we performed a two-sample Mendelian randomization (MR) analysis. Genetic instruments that reached genome-wide significance (p < 5 × 10 - 8) for risk factors were obtained from genome-wide association studies(GWASs) conducted on individuals of European origin. On the other hand, genetic instruments of AA, AAA, TAA or AD were chosen from the FinnGen cohort. The primary analysis employed the inverse-variance weighted MR method, while sensitivity analyses were conducted using MR-Egger, weighted median MR, MR pleiotropy residual sum and outlier, and Phenoscanner searching. In addition, we performed the MR-Egger intercept analysis to identify potential pleiotropy and utilized Cochran's Q statistics to evaluate heterogeneity. Additionally, we conducted bidirectional Mendelian randomization experiments to mitigate the potential influence of reverse causation. According to the results of our study, there were statistically significant higher risks for AA in relation to CAD/MI(odds ratio (OR) with 95% confidence interval (CI): 1.309 (1.150-1.490), and 1.255 (1.147-1.373). Similarly, there were statistically significant higher risks for AAA in relation to CAD and MI (OR with 95% CI: 1.383 (1.189-1.609), and 1.352 (1.178-1.552). The sensitivity analysis demonstrated that the causative effects of CAD/MI, and AA /AAA, were robust. A positive causal link was observed between CAD/MI, and AA/AAA. Nevertheless, no causal link was found between CAD, MI, urate levels, and TAA .

Fig. 1

Displays the estimated causal effects among CAD, MI, urate levels, and AA, as well as CAD, MI, and AAA, TAA, AD, utilizing various Mendelian randomization (MR) techniques.

Fig. 2

Displays the association among CAD/MI, urate levels, and AA/AAA/TAA.

Fig. 3

Presents the MR outcomes pertaining to CAD and AA. Subfigure A displays a scatter plot illustrating the genetic correlations between CAD and AA; Subfigure B showcases a forest plot of the causal effects of CAD associated SNPs on AA.Subfigure C showcases a leave-one-out plot of the causal effects of CAD associated SNPs on AA.Subfigure D showcases a funnel plot of the causal effects of CAD associated SNPs on AA.

Fig. 4

Presents the MR outcomes pertaining to MI and AA. Subfigure A displays a scatter plot illustrating the genetic correlations between MI and AA; Subfigure B showcases a forest plot of the causal effects of MI associated SNPs on AA.Subfigure C showcases a leave-one-out plot of the causal effects of MI associated SNPs on AA.Subfigure D showcases a funnel plot of the causal effects of MI associated SNPs on AA.

Fig. 5

Presents the MR outcomes pertaining to urate levels and AA. Subfigure A displays a scatter plot illustrating the genetic correlations between urate levels and AA; Subfigure B showcases a forest plot of the causal effects of urate levels associated SNPs on AA.Subfigure C showcases a leave-one-out plot of the causal effects of urate levels associated SNPs on AA.Subfigure D showcases a funnel plot of the causal effects of urate levels associated SNPs on AA.

Fig. 6

Presents the MR outcomes pertaining to CAD and AAA. Subfigure A displays a scatter plot illustrating the genetic correlations between CAD and AAA; Subfigure B showcases a forest plot of the causal effects of CAD associated SNPs on AAA.Subfigure C showcases a leave-one-out plot of the causal effects of CAD associated SNPs on AAA.Subfigure D showcases a funnel plot of the causal effects of CAD associated SNPs on AAA.

Fig. 7

Presents the MR outcomes pertaining to MI and AAA. Subfigure A displays a scatter plot illustrating the genetic correlations between MI and AAA; Subfigure B showcases a forest plot of the causal effects of MI associated SNPs on AAA.Subfigure C showcases a leave-one-out plot of the causal effects of MI associated SNPs on AAA.Subfigure D showcases a funnel plot of the causal effects of MI associated SNPs on AAA.