Epigenome-Wide Association Study Identifies Cardiac Gene Patterning and a Novel Class of Biomarkers for Heart Failure. Meder, B., Haas, J., Sedaghat-Hamedani, F., Kayvanpour, E., Frese, K., Lai, A., Nietsch, R., Scheiner, C., Mester, S., Bordalo, D. M., Amr, A., Dietrich, C., Pils, D., Siede, D., Hund, H., Bauer, A., Holzer, D. B., Ruhparwar, A., Mueller-Hennessen, M., Weichenhan, D., Plass, C., Weis, T., Backs, J., Wuerstle, M., Keller, A., Katus, H. A, & Posch, A. E Circulation, 136:1528–1544, October, 2017. doi abstract bibtex 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. 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. In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected ≤0.05), with 3 of them reaching epigenome-wide significance at ≤5×10 . 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. The present study provides to our knowledge the first epigenome-wide association study in living patients with heart failure using a multi-omics approach.
@Article{Meder2017,
author = {Meder, Benjamin and Haas, Jan and Sedaghat-Hamedani, Farbod and Kayvanpour, Elham and Frese, Karen and Lai, Alan and Nietsch, Rouven and Scheiner, Christina and Mester, Stefan and Bordalo, Diana Martins and Amr, Ali and Dietrich, Carsten and Pils, Dietmar and Siede, Dominik and Hund, Hauke and Bauer, Andrea and Holzer, Daniel Benjamin and Ruhparwar, Arjang and Mueller-Hennessen, Matthias and Weichenhan, Dieter and Plass, Christoph and Weis, Tanja and Backs, Johannes and Wuerstle, Maximilian and Keller, Andreas and Katus, Hugo A and Posch, Andreas E},
title = {Epigenome-Wide Association Study Identifies Cardiac Gene Patterning and a Novel Class of Biomarkers for Heart Failure.},
journal = {Circulation},
year = {2017},
volume = {136},
pages = {1528--1544},
month = oct,
issn = {1524-4539},
abstract = {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. 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. In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected ≤0.05), with 3 of them reaching epigenome-wide significance at ≤5×10 . 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. The present study provides to our knowledge the first epigenome-wide association study in living patients with heart failure using a multi-omics approach.},
chemicals = {Genetic Markers, RNA, Messenger},
citation-subset = {AIM, IM},
completed = {2017-10-24},
country = {United States},
doi = {10.1161/CIRCULATIONAHA.117.027355},
issn-linking = {0009-7322},
issue = {16},
keywords = {Cardiomyopathy, Dilated, blood, diagnosis, genetics; Case-Control Studies; CpG Islands; DNA Methylation; Epigenesis, Genetic; Epigenomics, methods; Gene Expression Profiling; Genetic Loci; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Heart Failure, blood, diagnosis, genetics; Heart Ventricles, chemistry; High-Throughput Nucleotide Sequencing; Humans; Phenotype; RNA, Messenger, genetics; Sequence Analysis, RNA; DNA methylation; biomarker; dilated cardiomyopathy; epigenetics; heart failure; natriuretic peptides},
nlm-id = {0147763},
owner = {NLM},
pii = {CIRCULATIONAHA.117.027355},
pmid = {28838933},
pubmodel = {Print-Electronic},
pubstatus = {ppublish},
revised = {2017-10-24},
}
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