Association between epigenetic aging and atrioventricular block: a two-sample Mendelian randomization study.

IF 3 4区医学 Q2 GENETICS & HEREDITY

Epigenomics Pub Date : 2025-01-20 DOI:10.1080/17501911.2025.2454894

Wanqian Pan, Chi Zhang, Xiaojiao Du, Xiong Su, Jia Lin, Tingbo Jiang, Weixiang Chen

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引用次数: 0

Abstract

Aims: Atrioventricular block (AVB) is a prevalent bradyarrhythmia. This study aims to investigate the causal effects of epigenetic aging, as inferred from DNA methylation profiles on the prevalence of AVB by Mendelian randomization (MR) analysis.

Methods: Genetic instruments for epigenetic aging and AVB were obtained from genome-wide association study data in the Edinburgh DataShare and FinnGen biobanks. Univariable and multivariable MR analyses were conducted to evaluate causal associations. Additionally, we employed sensitivity tests to assess the robustness of the MR findings.

Results: MR analysis showed that genetically predicted GrimAge acceleration was significantly associated with a higher risk of AVB (inverse variance-weighted: p = 0.010, 95% confidence interval (CI) = 1.024-1.196; weighted median: p = 0.031, 95% CI = 1.009-1.215). However, no evidence supported a causal relationship between AVB and epigenetic aging. The association between epigenetic aging and AVB was established using multivariate MR analysis after adjusting for various risk factors. Sensitivity analyses confirmed the reliability and robustness of the results.

Conclusion: Our findings suggest that epigenetic aging in GrimAge may increase the risk of AVB, emphasizing the importance of addressing epigenetic aging in strategies for AVB prevention.

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表观遗传衰老与房室传导阻滞之间的关系：一项双样本孟德尔随机化研究。

目的：房室传导阻滞（AVB）是一种常见的慢型心律失常。本研究旨在通过孟德尔随机化（MR）分析，从DNA甲基化谱推断表观遗传衰老对AVB患病率的因果影响。方法：从爱丁堡数据共享和FinnGen生物银行的全基因组关联研究数据中获得表观遗传衰老和AVB的遗传仪器。进行单变量和多变量MR分析以评估因果关系。此外，我们采用敏感性测试来评估MR结果的稳健性。结果：MR分析显示，基因预测的GrimAge加速与AVB高风险显著相关(方差加权倒数：p = 0.010, 95%可信区间(CI) = 1.024-1.196；加权中位数：p = 0.031, 95% CI = 1.009-1.215)。然而，没有证据支持AVB与表观遗传衰老之间的因果关系。在调整各种危险因素后，采用多变量MR分析确定表观遗传衰老与AVB之间的关联。敏感性分析证实了结果的可靠性和稳健性。结论：我们的研究结果表明，GrimAge的表观遗传衰老可能增加AVB的风险，强调了解决表观遗传衰老在AVB预防策略中的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Epigenomics GENETICS & HEREDITY-

CiteScore

5.80

自引率

2.60%

发文量

审稿时长

>12 weeks

期刊介绍： Epigenomics provides the forum to address the rapidly progressing research developments in this ever-expanding field; to report on the major challenges ahead and critical advances that are propelling the science forward. The journal delivers this information in concise, at-a-glance article formats – invaluable to a time constrained community. Substantial developments in our current knowledge and understanding of genomics and epigenetics are constantly being made, yet this field is still in its infancy. Epigenomics provides a critical overview of the latest and most significant advances as they unfold and explores their potential application in the clinical setting.