Related Experiment Video
Updated: Feb 24, 2026
Author Spotlight: Cardiac Cell Transgenesis for Rapid Gene Screening
Published on: May 24, 2024
Epigenome-Wide Association Study Identifies Cardiac Gene Patterning and a Novel Class of Biomarkers for Heart Failure
Benjamin Meder1, Jan Haas1, Farbod Sedaghat-Hamedani1
1From Department of Internal Medicine III, Institute for Cardiomyopathies, University of Heidelberg, Germany (B.M., J.H., F.S.-H., E.K., K.F., A.L., R.N., C.S., S.M., D.M.-B., A.A., H.H., D.B.H., M.M.-H., T.W., H.A.K.); Siemens Healthcare GmbH, Strategy and Innovation, Erlangen, Germany (C.D., M.W., A.E.P.); Department of Bioinformatics, University of Saarland, Saarbrücken, Germany (A.K.); German Centre for Cardiovascular Research, Berlin, Germany (B.M., J.H., F.S.-H., E.K., K.F., A.L., D.S., M.M.-H., T.W., J.B., H.A.K.); Institute for Molecular Cardiology and Epigenetics, University of Heidelberg, Germany (D.S., J.B.); Funktionelle Genomanalyse, Deutsches Krebsforschungszentrum, Heidelberg, Germany (A.B.); Department of Cardiac Surgery, University of Heidelberg, Germany (A.R.); Siemens AG, Corporate Technology, Vienna, Austria (D.P.); Section for Clinical Biometrics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Austria (D.P.); and Division of Epigenomics and Cancer Risk Factors, Deutsches Krebsforschungszentrum, Heidelberg, Germany (D.W., C.P.).
Background:
Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls.
Methods:
Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands. RNA deep sequencing was performed on the same samples in parallel. Whole-genome sequencing of all patients allowed exclusion of promiscuous genotype-induced methylation calls.
Results:
In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected P≤0.05), with 3 of them reaching epigenome-wide significance at P≤5×10-8. Twenty-seven (46%) of these loci could be replicated in independent cohorts, underlining the role of epigenetic regulation of key cardiac transcription regulators. Using a staged multi-omics study design, we link a subset of 517 epigenetic loci with dilated cardiomyopathy and cardiac gene expression. Furthermore, we identified distinct epigenetic methylation patterns that are conserved across tissues, rendering these CpGs novel epigenetic biomarkers for heart failure.
Conclusions:
The present study provides to our knowledge the first epigenome-wide association study in living patients with heart failure using a multi-omics approach.
More Related Videos
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
01:17Pathophysiology of Heart Failure
01:29Heart Failure II: Pathophysiology
01:29Pharmacogenomics: Identification of New Drug Targets
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy