Department of Emergency, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.
, No. 68, Qinglong Street, Qingyang District, Chengdu, Sichuan, China.
Sci Rep. 2024 Oct 14;14(1):24070. doi: 10.1038/s41598-024-75367-4.
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 .
本研究旨在探讨冠状动脉疾病（CAD）、心肌梗死（MI）、尿酸水平与主动脉瘤（AA）、腹主动脉瘤（AAA）、胸主动脉瘤（TAA）、主动脉夹层（AD）在欧洲血统个体中的潜在因果关系。为了分别检验 CAD、MI 和尿酸水平与 AA、AAA、TAA 和 AD 之间的潜在因果关系，我们进行了两样本孟德尔随机化（MR）分析。用于风险因素的遗传工具是从欧洲起源的个体进行的全基因组关联研究（GWAS）中获得的，达到了全基因组显著水平（p < 5 × 10-8）。另一方面，AA、AAA、TAA 或 AD 的遗传工具是从芬兰人队列中选择的。主要分析采用逆方差加权 MR 方法，同时使用 MR-Egger、加权中位数 MR、MR 多效性残差和异常值以及 Phenoscanner 搜索进行敏感性分析。此外，我们进行了 MR-Egger 截距分析以识别潜在的多效性，并使用 Cochran 的 Q 统计量评估异质性。此外，我们进行了双向孟德尔随机化实验，以减轻潜在的反向因果关系的影响。根据我们的研究结果，CAD/MI 与 AA 之间存在统计学上显著的更高风险（比值比（OR）和 95%置信区间（CI）：1.309（1.150-1.490）和 1.255（1.147-1.373）。同样，CAD 与 AAA 之间存在统计学上显著的更高风险（OR 和 95% CI：1.383（1.189-1.609）和 1.352（1.178-1.552）。敏感性分析表明，CAD/MI 和 AA/AAA 的因果作用是稳健的。CAD/MI 和 AA/AAA 之间存在正向因果关系。然而，CAD、MI、尿酸水平和 TAA 之间没有发现因果关系。
