Epigenetic Contributions to Clinical Risk Prediction of Cardiovascular Disease.

IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Circulation: Genomic and Precision Medicine Pub Date : 2024-02-01 Epub Date: 2024-01-30 DOI:10.1161/CIRCGEN.123.004265
Aleksandra D Chybowska, Danni A Gadd, Yipeng Cheng, Elena Bernabeu, Archie Campbell, Rosie M Walker, Andrew M McIntosh, Nicola Wrobel, Lee Murphy, Paul Welsh, Naveed Sattar, Jackie F Price, Daniel L McCartney, Kathryn L Evans, Riccardo E Marioni
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Abstract

Background: Cardiovascular disease (CVD) is among the leading causes of death worldwide. The discovery of new omics biomarkers could help to improve risk stratification algorithms and expand our understanding of molecular pathways contributing to the disease. Here, ASSIGN-a cardiovascular risk prediction tool recommended for use in Scotland-was examined in tandem with epigenetic and proteomic features in risk prediction models in ≥12 657 participants from the Generation Scotland cohort.

Methods: Previously generated DNA methylation-derived epigenetic scores (EpiScores) for 109 protein levels were considered, in addition to both measured levels and an EpiScore for cTnI (cardiac troponin I). The associations between individual protein EpiScores and the CVD risk were examined using Cox regression (ncases≥1274; ncontrols≥11 383) and visualized in a tailored R application. Splitting the cohort into independent training (n=6880) and test (n=3659) subsets, a composite CVD EpiScore was then developed.

Results: Sixty-five protein EpiScores were associated with incident CVD independently of ASSIGN and the measured concentration of cTnI (P<0.05), over a follow-up of up to 16 years of electronic health record linkage. The most significant EpiScores were for proteins involved in metabolic, immune response, and tissue development/regeneration pathways. A composite CVD EpiScore (based on 45 protein EpiScores) was a significant predictor of CVD risk independent of ASSIGN and the concentration of cTnI (hazard ratio, 1.32; P=3.7×10-3; 0.3% increase in C-statistic).

Conclusions: EpiScores for circulating protein levels are associated with CVD risk independent of traditional risk factors and may increase our understanding of the etiology of the disease.

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表观遗传学对心血管疾病临床风险预测的贡献。
背景:心血管疾病(CVD)是导致全球死亡的主要原因之一。新的全息生物标志物的发现有助于改善风险分层算法,扩大我们对导致该疾病的分子途径的了解。在此,我们对 ASSIGN(一种推荐在苏格兰使用的心血管风险预测工具)与风险预测模型中的表观遗传学和蛋白质组特征进行了研究,研究对象是来自苏格兰一代队列的≥12 657 名参与者:除了cTnI(心肌肌钙蛋白I)的测量水平和EpiScore外,还考虑了之前生成的109种蛋白质水平的DNA甲基化衍生表观遗传学评分(EpiScores)。我们使用 Cox 回归(ncases≥1274;ncontrols≥11 383)检验了单个蛋白质 EpiScores 与心血管疾病风险之间的关系,并在定制的 R 应用程序中将其可视化。将队列分成独立的训练子集(n=6880)和测试子集(n=3659),然后开发出综合心血管疾病 EpiScore:结果:65个蛋白质EpiScore与心血管疾病的发生相关,与ASSIGN和cTnI的测量浓度无关(PP=3.7×10-3;C统计量增加0.3%):循环蛋白水平的 EpiScores 与心血管疾病风险相关,不受传统风险因素的影响,可加深我们对心血管疾病病因的了解。
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来源期刊
Circulation: Genomic and Precision Medicine
Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
9.20
自引率
5.40%
发文量
144
期刊介绍: Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
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