Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2023 Jun 2;14:1175890. doi: 10.3389/fimmu.2023.1175890. eCollection 2023.
In observational and experimental studies, allergic diseases (AD) have been reported to be associated with some types of cardiovascular diseases (CVD), as both share common pathophysiological processes involving inflammation and metabolic disorders. However, the direction of the causal association between them remains unclear. This Mendelian randomization (MR) study aims to examine the bidirectional causality between AD and CVD.
We utilized publicly available genome-wide association study (GWAS) summary statistics data from European participants in the UK Biobank and the IEU Open GWAS database. Genetic variants associated with AD, asthma, and CVD were identified and used as instrumental variables to investigate the genetically causal association between them. MR analyses were performed using various analytical methods, including inverse variance weighted-fixed effects (IVW-FE), inverse variance weighted-multiplicative random effects (IVW-RE), MR-Egger, weighted median, weighted mode, and maximum likelihood. Sensitivity tests were conducted to assess the validity of the causality.
The MR analysis with the IVW method revealed a genetically predicted association between AD and essential hypertension [odds ratio (OR)=0.9987, 95% confidence interval (CI): 0.9976-0.9998, P=0.024], as well as between asthma and atrial fibrillation (OR=1.001, 95% CI: 1.0004-1.0017, P=6.43E-05). In the reverse MR analyses, heart failure was associated with allergic diseases (OR=0.0045, 95% CI: 1.1890E-04 - 0.1695, P=0.004), while atherosclerosis (OR=8.7371E-08, 95% CI: 1.8794E-14 - 4.0617E-01, P=0.038) and aortic aneurysm and dissection (OR=1.7367E-07, 95% CI: 3.8390E-14 - 7.8567E-01, P=0.046) might be protective factors of asthma. However, after a Bonferroni correction, only the association between asthma and atrial fibrillation remained robust.
The MR study revealed that asthma is a predominant risk of atrial fibrillation in European individuals, consistent with most experimental and observational studies. Whether AD affects other CVD and the causality between them needs further investigation.
在观察性和实验性研究中，过敏性疾病（AD）与某些类型的心血管疾病（CVD）有关，因为两者都存在涉及炎症和代谢紊乱的共同病理生理过程。然而，它们之间因果关系的方向仍不清楚。这项孟德尔随机化（MR）研究旨在研究 AD 和 CVD 之间的双向因果关系。
我们利用英国生物库和 IEU 开放 GWAS 数据库中欧洲参与者的公开全基因组关联研究（GWAS）汇总统计数据，确定与 AD、哮喘和 CVD 相关的遗传变异，并将其用作工具变量，以研究它们之间的遗传因果关系。使用各种分析方法（包括逆方差加权固定效应（IVW-FE）、逆方差加权乘法随机效应（IVW-RE）、MR-Egger、加权中位数、加权模式和最大似然）进行 MR 分析。进行敏感性测试以评估因果关系的有效性。
使用 IVW 方法的 MR 分析显示，AD 与原发性高血压之间存在遗传预测相关性[比值比（OR）=0.9987，95%置信区间（CI）：0.9976-0.9998，P=0.024]，哮喘与心房颤动之间也存在相关性（OR=1.001，95%CI：1.0004-1.0017，P=6.43E-05）。在反向 MR 分析中，心力衰竭与过敏性疾病相关（OR=0.0045，95%CI：1.1890E-04-0.1695，P=0.004），而动脉粥样硬化（OR=8.7371E-08，95%CI：1.8794E-14-4.0617E-01，P=0.038）和主动脉瘤和夹层（OR=1.7367E-07，95%CI：3.8390E-14-7.8567E-01，P=0.046）可能是哮喘的保护因素。然而，在进行 Bonferroni 校正后，只有哮喘与心房颤动之间的关联仍然稳健。
MR 研究表明，哮喘是欧洲人群心房颤动的主要危险因素，与大多数实验和观察性研究一致。AD 是否会影响其他 CVD 以及它们之间的因果关系仍需要进一步研究。
