Causal effects of cardiovascular health on five epigenetic clocks.

IF 5.4 3区材料科学 Q2 CHEMISTRY, PHYSICAL

ACS Applied Energy Materials Pub Date : 2024-09-27 DOI:10.1186/s13148-024-01752-5

Hsien-Liang Sung, Wan-Yu Lin

{"title":"Causal effects of cardiovascular health on five epigenetic clocks.","authors":"Hsien-Liang Sung, Wan-Yu Lin","doi":"10.1186/s13148-024-01752-5","DOIUrl":null,"url":null,"abstract":"Background: 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.Methods and results: 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.Conclusions: 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.","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438310/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Energy Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13148-024-01752-5","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: 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.

Methods and results: 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.

Conclusions: 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.

查看原文本刊更多论文

心血管健康对五个表观遗传时钟的因果效应。

背景：这项研究探讨了心血管健康（CVH）与衰老之间的关系。以往的研究表明，理想的心血管健康与衰老速度（通过表观遗传年龄加速度（EAA）测量）的减缓有关。然而，CVH 与 EAA 之间的因果关系仍有待探索：我们利用台湾生物库数据对（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，我们采用两阶段最小二乘法对2383名参与者进行了单样本孟德尔随机化（MR）分析，以检验（12点）CVH评分与EAA之间的因果关系。结果，我们观察到 CVH 评分对 GrimAge 加速（GrimEAA）（β [SE]：- 0.993 [0.363] 年；p = 0.0063）和基于 DNA 甲基化的纤溶酶原激活剂抑制剂-1（DNAmPAI-1）（β [SE]：- 0.294 [0.099] DNAmPAI-1 标准差（sd）；p = 0.0030）具有显著的因果效应。深入挖掘单个 CVH 成分，理想总胆固醇得分（0 [差]、1 [中等] 或 2 [理想]）与 DNAmPAI-1 存在因果关系（β [SE]：- 0.452 [0.150] sd of DNAmPAI-1；假发现率 [FDR] q = 0.0102）。理想体重指数（BMI）得分与 GrimEAA（β [SE]：- 2.382 [0.952] 年；FDR q = 0.0498）和 DunedinPACE（β [SE]：- 0.097 [0.030]；FDR q = 0.0044）存在因果关系。我们还使用欧洲 GWAS 的汇总统计数据进行了双样本 MR 分析。我们发现，（12 点）CVH 评分对 Horvath 的内在表观遗传年龄加速度（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，我们还检测到体重指数（β [SE]：0.599 [0.081] 年；q = 2.91E-12）、从不吸烟（β [SE]：- 2.981 [0.524] 年；q = 1.63E-7）、步行（β [SE]：- 4.313 [1.236] 年；q = 0.004）和干果摄入量（β [SE]：- 1.523 [0.504] 年；q = 0.013）对欧洲人群 GrimEAA 的影响：我们的研究证实了保持理想的 CVH 与表观遗传年龄之间的因果关系。结论：我们的研究证实了保持理想的 CVH 与表观遗传年龄之间的因果关系，这为个人改善健康状况、延缓衰老提供了切实可行的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Applied Energy Materials Materials Science-Materials Chemistry

CiteScore

10.30

自引率

6.20%

发文量

1368

期刊介绍： ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.