Cardiovascular disease biomarkers derived from circulating cell-free DNA methylation

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Item Type:

Article

Title:

Cardiovascular disease biomarkers derived from circulating cell-free DNA methylation

Creators Name:

Cuadrat, R.R.C. and Kratzer, A. and Arnal, H.G. and Rathgeber, A.C. and Wreczycka, K. and Blume, A. and Gündüz, I.B. and Ebenal, V. and Mauno, T. and Osberg, B. and Moobed, M. and Hartung, J. and Jakobs, K. and Seppelt, C. and Meteva, D. and Haghikia, A. and Leistner, D.M. and Landmesser, Ulf and Akalin, A.

Abstract:

Acute coronary syndrome (ACS) remains a major cause of worldwide mortality. The syndrome occurs when blood flow to the heart muscle is decreased or blocked, causing muscle tissues to die or malfunction. There are three main types of ACS: Non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, and unstable angina. The treatment depends on the type of ACS, and this is decided by a combination of clinical findings, such as electrocardiogram and plasma biomarkers. Circulating cell-free DNA (ccfDNA) is proposed as an additional marker for ACS since the damaged tissues can release DNA to the bloodstream. We used ccfDNA methylation profiles for differentiating between the ACS types and provided computational tools to repeat similar analysis for other diseases. We leveraged cell type specificity of DNA methylation to deconvolute the ccfDNA cell types of origin and to find methylation-based biomarkers that stratify patients. We identified hundreds of methylation markers associated with ACS types and validated them in an independent cohort. Many such markers were associated with genes involved in cardiovascular conditions and inflammation. ccfDNA methylation showed promise as a non-invasive diagnostic for acute coronary events. These methods are not limited to acute events, and may be used for chronic cardiovascular diseases as well.

Source:

NAR Genomics and Bioinformatics

ISSN:

2631-9268

Publisher:

Oxford University Press

Volume:

Number:

Page Range:

lqad061

Date:

June 2023