Department of Cardiovascular Medicine, The First People's Hospital of Shangqiu, Shangqiu 476000, China.
Graduate School, Dalian Medical University, Dalian, 116044, China.
Glob Heart. 2024 May 14;19(1):48. doi: 10.5334/gh.1324. eCollection 2024.
There is growing evidence that concentrations of DNA methylation are associated with cardiovascular disease; however, it is unclear whether this association reflects a causal relationship.
We utilized a two-sample Mendelian randomization (MR) approach to investigate whether DNA methylation can affect the risk of developing cardiovascular disease in human life. We primarily performed the inverse variance weighted (IVW) method to analyze the causal effect of DNA methylation on multiple cardiovascular diseases. Additionally, to ensure the robustness of our findings, we conducted several sensitivity analyses using alternative methodologies. These analysis methods included maximum likelihood, MR-Egger regression, weighted median method, and weighted model methods.
Inverse variance weighted estimates suggested that an SD increase in DNA methylation Hannum age acceleration exposure increased the risk of cardiac arrhythmias (OR = 1.03, 95% CI 1.00-1.05, = 0.0290) and atrial fibrillation (OR = 1.03, 95% CI 1.00-1.05, = 0.0022). We also found that an SD increase in DNA methylation PhenoAge acceleration exposure increased the risk of heart failure (OR = 1.01, 95% CI 1.00-1.03, = 0.0362). Exposure to DNA methylation-estimated granulocyte proportions was found to increase the risk of hypertension (OR = 1.00, 95% CI 1.00-1.0001, p = 0.0291). Exposure to DNA methylation-estimated plasminogen activator inhibitor-1 levels was found to increase the risk of heart failure (OR = 1.00, 95% CI 1.00-1.00, = 0.0215).
This study reveals a causal relationship between DNA methylation and CVD. Exposed to high levels of DNA methylation Hannum age acceleration inhabitants with an increased risk of cardiac arrhythmias and atrial fibrillation. DNA methylation PhenoAge acceleration levels exposure levels were positively associated with the increased risk of developing heart failure. This has important implications for the prevention of cardiovascular diseases.
越来越多的证据表明，DNA 甲基化浓度与心血管疾病有关；然而，目前尚不清楚这种关联是否反映了因果关系。
我们利用两样本 Mendelian 随机化（MR）方法来研究 DNA 甲基化是否可以影响人类生命中患心血管疾病的风险。我们主要使用逆方差加权（IVW）方法来分析 DNA 甲基化对多种心血管疾病的因果影响。此外，为了确保我们研究结果的稳健性，我们还使用替代方法学进行了几项敏感性分析。这些分析方法包括最大似然法、MR-Egger 回归法、加权中位数法和加权模型法。
逆方差加权估计表明，DNA 甲基化 Hannum 年龄加速暴露每增加一个标准差，心律失常（OR=1.03，95%CI 1.00-1.05， = 0.0290）和心房颤动（OR=1.03，95%CI 1.00-1.05， = 0.0022）的风险增加。我们还发现，DNA 甲基化 PhenoAge 加速暴露每增加一个标准差，心力衰竭（OR=1.01，95%CI 1.00-1.03， = 0.0362）的风险增加。暴露于 DNA 甲基化估计的嗜中性粒细胞比例增加高血压（OR=1.00，95%CI 1.00-1.0001，p=0.0291）的风险。暴露于 DNA 甲基化估计的纤溶酶原激活物抑制剂-1 水平增加心力衰竭（OR=1.00，95%CI 1.00-1.00， = 0.0215）的风险。
这项研究揭示了 DNA 甲基化与 CVD 之间的因果关系。暴露于高水平的 DNA 甲基化 Hannum 年龄加速居民患心律失常和心房颤动的风险增加。DNA 甲基化 PhenoAge 加速水平暴露与心力衰竭风险增加呈正相关。这对心血管疾病的预防具有重要意义。
