Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Room 501, No. 17, Xu-Zhou Road, Taipei, 100, Taiwan.
Master of Public Health Degree Program, College of Public Health, National Taiwan University, Taipei, Taiwan.
Clin Epigenetics. 2024 Sep 27;16(1):134. doi: 10.1186/s13148-024-01752-5.
This work delves into the relationship between cardiovascular health (CVH) and aging. Previous studies have shown an association of ideal CVH with a slower aging rate, measured by epigenetic age acceleration (EAA). However, the causal relationship between CVH and EAA has remained unexplored.
We performed genome-wide association studies (GWAS) on the (12-point) CVH score and its components using the Taiwan Biobank data, in which weighted genetic risk scores were treated as instrumental variables. Subsequently, we conducted a one-sample Mendelian Randomization (MR) analysis with the two-stage least-squares method on 2383 participants to examine the causal relationship between the (12-point) CVH score and EAA. As a result, we observed a significant causal effect of the CVH score on GrimAge acceleration (GrimEAA) (β [SE]: - 0.993 [0.363] year; p = 0.0063) and DNA methylation-based plasminogen activator inhibitor-1 (DNAmPAI-1) (β [SE]: - 0.294 [0.099] standard deviation (sd) of DNAmPAI-1; p = 0.0030). Digging individual CVH components in depth, the ideal total cholesterol score (0 [poor], 1 [intermediate], or 2 [ideal]) was causally associated with DNAmPAI-1 (β [SE]: - 0.452 [0.150] sd of DNAmPAI-1; false discovery rate [FDR] q = 0.0102). The ideal body mass index (BMI) score was causally associated with GrimEAA (β [SE]: - 2.382 [0.952] years; FDR q = 0.0498) and DunedinPACE (β [SE]: - 0.097 [0.030]; FDR q = 0.0044). We also performed a two-sample MR analysis using the summary statistics from European GWAS. We observed that the (12-point) CVH score exhibits a significant causal effect on Horvath's intrinsic epigenetic age acceleration (β [SE]: - 0.389 [0.186] years; p = 0.036) and GrimEAA (β [SE]: - 0.526 [0.244] years; p = 0.031). Furthermore, we detected causal effects of BMI (β [SE]: 0.599 [0.081] years; q = 2.91E-12), never smoking (β [SE]: - 2.981 [0.524] years; q = 1.63E-7), walking (β [SE]: - 4.313 [1.236] years; q = 0.004), and dried fruit intake (β [SE]: - 1.523 [0.504] years; q = 0.013) on GrimEAA in the European population.
Our research confirms the causal link between maintaining an ideal CVH and epigenetic age. It provides a tangible pathway for individuals to improve their health and potentially slow aging.
本研究探讨了心血管健康（CVH）与衰老之间的关系。先前的研究表明，理想的 CVH 与表观遗传年龄加速（EAA）的衰老速度较慢有关。然而，CVH 和 EAA 之间的因果关系仍未得到探索。
我们使用台湾生物银行的数据对（12 分）CVH 评分及其组成部分进行了全基因组关联研究（GWAS），其中加权遗传风险评分被视为工具变量。随后，我们使用两阶段最小二乘法在 2383 名参与者中进行了单样本孟德尔随机化（MR）分析，以检验（12 分）CVH 评分与 EAA 之间的因果关系。结果表明，CVH 评分对 GrimAge 加速（GrimEAA）（β[SE]：-0.993[0.363]岁；p=0.0063）和基于 DNA 甲基化的纤溶酶原激活物抑制剂-1（DNAmPAI-1）（β[SE]：-0.294[0.099]个 DNAmPAI-1 的标准偏差；p=0.0030）有显著的因果效应。深入挖掘个体 CVH 成分，理想的总胆固醇评分（0[差]、1[中等]或 2[理想]）与 DNAmPAI-1 呈因果关系（β[SE]：-0.452[0.150]个 DNAmPAI-1 的标准偏差；假发现率[FDR]q=0.0102）。理想的体重指数（BMI）评分与 GrimEAA 呈因果关系（β[SE]：-2.382[0.952]岁；FDR q=0.0498）和 DunedinPACE（β[SE]：-0.097[0.030]；FDR q=0.0044）。我们还使用欧洲 GWAS 的汇总统计数据进行了两样本 MR 分析。我们发现，（12 分）CVH 评分对 Horvath 的内在表观遗传年龄加速（β[SE]：-0.389[0.186]岁；p=0.036）和 GrimEAA（β[SE]：-0.526[0.244]岁；p=0.031）有显著的因果效应。此外，我们还检测到 BMI（β[SE]：0.599[0.081]岁；q=2.91E-12）、从不吸烟（β[SE]：-2.981[0.524]岁；q=1.63E-7）、步行（β[SE]：-4.313[1.236]岁；q=0.004）和干果摄入（β[SE]：-1.523[0.504]岁；q=0.013）对欧洲人群 GrimEAA 的因果效应。
本研究证实了保持理想 CVH 与表观遗传年龄之间的因果关系。它为个人改善健康状况和潜在延缓衰老提供了一个切实可行的途径。
