Department of Emergency Medicine, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People's Republic of China.
Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, 6027, Australia.
BMC Cardiovasc Disord. 2022 Jun 11;22(1):262. doi: 10.1186/s12872-022-02702-w.
Previous studies have observed inconsistent associations between coronavirus disease 2019 (COVID-19) and heart failure (HF), but these studies were prone to bias based on reverse causality and residual confounding factors. We aimed to investigate genetic liability between COVID-19 and heart failure using a bidirectional Mendelian randomization study.
The causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and HF are determined by using a bidirectional Mendelian randomization analysis. We drew on summary statistics from the largest HF genome-wide association study (GWAS) meta-analysis on individuals of European ancestry, which included 47,309 HF patients and 930,014 controls. The inverse variance weighted (IVW), an adaption of the Egger regression (MR-Egger), the weighted median, and weighted model were conducted for the Mendelian randomization analysis to estimate a causal effect. To confirm the stability, we performed a "leave-one-out" approach for the sensitivity analysis.
Genetically predicted severe COVID-19 was not significantly associated with the risk of HF [odds ratio (OR), 1.003; 95% confidence interval (CI), 0.969-1.037; p = 0.867]. The IVW demonstrated that there was no association between genetically hospitalized COVID-19 infection and HF risk [OR, 1.009; 95% CI, 0.939-1.085; p = 0.797]. There was no evidence to support the association between genetically determined COVID-19 and the risk of HF [OR, 1.066; 95% CI, 0.955-1.190; p = 0.253]. In addition, genetically predicted HF was also not causally associated with COVID-19 [OR, 1.162; 95% CI, 0.824-1.639; p = 0.393]. MR-Egger analysis indicated no evidence of directional pleiotropy.
The current bidirectional Mendelian randomization analysis overcomes the limitations of observational studies. Our findings indicated that there is no causal association between COVID-19 and HF.
先前的研究观察到 2019 年冠状病毒病（COVID-19）与心力衰竭（HF）之间的关联不一致，但这些研究容易受到反向因果关系和残留混杂因素的影响。我们旨在使用双向 Mendelian 随机化研究来研究 COVID-19 与心力衰竭之间的遗传易感性。
使用双向 Mendelian 随机化分析确定 COVID-19（包括 COVID-19、与普通人群相比住院的 COVID-19 和严重 COVID-19）与 HF 之间的因果关系。我们利用欧洲血统个体中最大的心力衰竭全基因组关联研究（GWAS）荟萃分析的汇总统计数据，其中包括 47,309 例心力衰竭患者和 930,014 例对照。进行逆方差加权（IVW）、Egger 回归（MR-Egger）的改编、加权中位数和加权模型的 Mendelian 随机化分析，以估计因果效应。为了确认稳定性，我们进行了敏感性分析的“逐一剔除”方法。
遗传预测的严重 COVID-19 与 HF 风险无显著相关性[比值比（OR），1.003；95%置信区间（CI），0.969-1.037；p=0.867]。IVW 表明，遗传住院 COVID-19 感染与 HF 风险之间没有关联[OR，1.009；95%CI，0.939-1.085；p=0.797]。没有证据支持遗传确定的 COVID-19 与 HF 风险之间的关联[OR，1.066；95%CI，0.955-1.190；p=0.253]。此外，遗传预测的 HF 也与 COVID-19 无因果关系[OR，1.162；95%CI，0.824-1.639；p=0.393]。MR-Egger 分析表明没有定向 pleiotropy 的证据。
当前的双向 Mendelian 随机化分析克服了观察性研究的局限性。我们的研究结果表明，COVID-19 与 HF 之间没有因果关系。
