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Ward-Caviness, C.K. ; Agha, G.* ; Chen, B.H.* ; Pfeiffer, L. ; Wilson, R. ; Wolf, P. ; Gieger, C. ; Schwartz, J.* ; Vokonas, P.S.* ; Hou, L.* ; Just, A.C.* ; Bandinelli, S.* ; Hernandez, D.G.* ; Singleton, A.B.* ; Prokisch, H. ; Meitinger, T. ; Kastenmüller, G. ; Ferrucci, L.* ; Baccarelli, A.A.* ; Waldenberger, M. ; Peters, A.

Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction.

Clin. Epigenet. 10:161 (2018)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BackgroundMost research into myocardial infarctions (MIs) have focused on preventative efforts. For survivors, the occurrence of an MI represents a major clinical event that can have long-lasting consequences. There has been little to no research into the molecular changes that can occur as a result of an incident MI. Here, we use three cohorts to identify epigenetic changes that are indicative of an incident MI and their association with gene expression and metabolomics.ResultsUsing paired samples from the KORA cohort, we screened for DNA methylation loci (CpGs) whose change in methylation is potentially indicative of the occurrence of an incident MI between the baseline and follow-up exams. We used paired samples from the NAS cohort to identify 11 CpGs which were predictive in an independent cohort. After removing two CpGs associated with medication usage, we were left with an epigenetic fingerprint of MI composed of nine CpGs. We tested this fingerprint in the InCHIANTI cohort where it moderately discriminated incident MI occurrence (AUC=0.61, P=6.5x10(-3)). Returning to KORA, we associated the epigenetic fingerprint loci with cis-gene expression and integrated it into a gene expression-metabolomic network, which revealed links between the epigenetic fingerprint CpGs and branched chain amino acid (BCAA) metabolism.ConclusionsThere are significant changes in DNA methylation after an incident MI. Nine of these CpGs show consistent changes in multiple cohorts, significantly discriminate MI in independent cohorts, and were independent of medication usage. Integration with gene expression and metabolomics data indicates a link between MI-associated epigenetic changes and BCAA metabolism.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Myocardial Infarction ; Dna Methylation ; Epigenetics ; Fingerprint ; Epigenetic Fingerprint ; Metabolites ; Branched Chain Amino Acid Metabolism ; Systems Biology; Coronary-artery-disease; Branched-chain; Diabetes-mellitus; Heart-disease; Amino-acids; Risk; Association; Gene; Metabolism; Desmosterol
ISSN (print) / ISBN 1868-7075
e-ISSN 1868-7083
Zeitschrift Clinical Epigenetics
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 161 Supplement: ,
Verlag Springer
Verlagsort Berlin : Heidelberg
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Institute of Human Genetics (IHG)
Institute of Bioinformatics and Systems Biology (IBIS)