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表观遗传对临床风险的贡献预测心血管疾病的风险

Aleksandra D Chybowska¹, Danni A Gadd¹, Yipeng Cheng¹

¹Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A.D.C., D.A.G., Y.C., E.B., A.C., D.L.M., K.L.E., R.E.M.), The University of Edinburgh, United Kingdom.

Circulation. Genomic and precision medicine

|January 30, 2024

概括

蛋白质水平的新表观遗传分数 (EpiScores) 在预测心血管疾病 (CVD) 风险方面表现有前途. 这些新型生物标志物可能会增强当前的风险评估工具,并加深我们对心血管疾病发展的理解.

科学领域:

基因组学和蛋白质组学
生物标志物发现发现
心血管疾病研究研究

背景情况:

心血管疾病 (CVD) 仍然是全球主要的死亡原因.
对于改善心血管疾病风险分层和了解疾病机制,omics生物标志物的进步至关重要.
这项研究评估了ASSIGN心血管风险预测工具以及大型队列中的表观遗传和蛋白质组数据.

研究的目的:

研究DNA甲基化衍生表观遗传分数 (EpiScores) 对蛋白质水平在预测心血管疾病 (CVD) 风险方面的有用性.
评估这些EpiScores是否提供了超越现有的风险预测工具 (如ASSIGN和心脏托罗邦素I (cTnI) 水平) 的附加值.
为增强风险预测开发一个复合CVDEpiScore.

主要方法:

使用先前生成的EpiScores用于109种蛋白质和测量水平,再加上cTnI的EpiScore.
采用考克斯回归分析来检查蛋白质EpiScores与心血管疾病风险之间的关联在一个大队列中 (n_cases ≥1274; n_controls ≥11,383).
使用苏格兰一代队列的独立培训和测试子集开发了一个复合的CVDEpiScore.

主要成果:

在16年的随访中,65个蛋白质EpiScore独立地与发生心血管疾病有关 (P<0.05).
关键相关蛋白质参与了代谢,免疫反应和组织发育/再生途径.
一个由45个蛋白质EpiScores衍生的复合CVDEpiScore,在独立于ASSIGN和cTnI (HR,1.32;P=3.7×10−3) 的情况下,显著预测了CVD风险,使C-统计数据提高了0.3%.

结论:

循环蛋白的EpiScore与心血管疾病风险有关,独立于传统的风险因素.
这些基于蛋白质的EpiScores可能会为心血管疾病的潜在病因提供新的见解.
这些发现表明,EpiScores可能是对心血管疾病风险评估策略的有价值补充.

关键词:

生物标志物生物标志物心血管疾病心血管疾病在表观基因组学上,表观基因组学.多种多种多种多种多种多种多种多种多种多种.这种药物是热素 (troponin).

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