Affordable Access

Access to the full text

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

Authors
  • Ward-Caviness, Cavin K.1
  • Agha, Golareh2
  • Chen, Brian H.3
  • Pfeiffer, Liliane4
  • Wilson, Rory4
  • Wolf, Petra5
  • Gieger, Christian4
  • Schwartz, Joel6
  • Vokonas, Pantel S.7, 8
  • Hou, Lifang9, 10
  • Just, Allan C.11
  • Bandinelli, Stefania12
  • Hernandez, Dena G.13
  • Singleton, Andrew B.13
  • Prokisch, Holger5, 14
  • Meitinger, Thomas5, 14, 15
  • Kastenmüller, Gabi16
  • Ferrucci, Luigi3
  • Baccarelli, Andrea A.2
  • Waldenberger, Melanie4
    • And 1 more
  • 1 Helmholtz Zentrum München, Institute of Epidemiology II, Ingolstädter Landstraβe 1, Neuherberg, 85764, Germany , Neuherberg (Germany)
  • 2 Columbia University, Mailman School of Public Health, 722 W 168th St, New York, NY, 10032, USA , New York (United States)
  • 3 National Institutes of Health, Longitudinal Studies Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, Baltimore, MD, 21224, USA , Baltimore (United States)
  • 4 Helmholtz Zentrum München, Research Unit Molecular Epidemiology, Ingolstädter Landstraβe 1, Neuherberg, 85764, Germany , Neuherberg (Germany)
  • 5 Helmholtz Zentrum München, Institute of Human Genetics, Ingolstädter Landstraβe 1, Neuherberg, 85764, Germany , Neuherberg (Germany)
  • 6 Harvard T.H. Chan School of Public Health, Department of Epidemiology, 677 Huntington Ave, Boston, MA, 02115, USA , Boston (United States)
  • 7 Boston University School of Medicine, VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston, MA, USA , Boston (United States)
  • 8 Boston University School of Medicine, Department of Medicine, 72 E Concord St, Boston, MA, 02118, USA , Boston (United States)
  • 9 Northwestern University, Department of Preventive Medicine, Feinberg School of Medicine, 680 N Lake Shore Dr, Chicago, IL, 60611, USA , Chicago (United States)
  • 10 Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 675 N. St. Clair, Chicago, IL, 60611, USA , Chicago (United States)
  • 11 Icahn School of Medicine at Mount Sinai, Department of Preventive Medicine, 1468 Madison Ave, New York, NY, 10029, USA , New York (United States)
  • 12 Azienda Sanitaria Firenze, Geriatric Rehabilitation Unit, Via del Cassero 19, San Casciano in Val di pesa, Florence, 50026, Italy , Florence (Italy)
  • 13 National Institutes of Health, Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, MD, 20814, USA , Bethesda (United States)
  • 14 Technische Universität München, Institut für Humangenetik, Arcistrasse 12, Munich, 80333, Germany , Munich (Germany)
  • 15 DZHK (German Center for Cardiovascular Disease), partner site Munich Heart Alliance, Munich, Germany , Munich (Germany)
  • 16 Helmholtz Zentrum München, Institute of Bioinformatics and Systems Biology, Ingolstädter Landstraβe 1, Neuherberg, 85764, Germany , Neuherberg (Germany)
Type
Published Article
Journal
Clinical Epigenetics
Publisher
Springer-Verlag
Publication Date
Dec 27, 2018
Volume
10
Issue
1
Identifiers
DOI: 10.1186/s13148-018-0588-7
Source
Springer Nature
Keywords
License
Green

Abstract

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 = 6.5 × 10−3). 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.

Report this publication

Statistics

Seen <100 times