Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction
Year: 2018
Type: article
Study design: Observational Study
Abstract: Most 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. Using 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. There 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.
Source: Clinical Epigenetics
Authors: Cavin K. Ward-Caviness, Golareh Agha, Brian H. Chen, Liliane Pfeiffer, Rory Wilson, Petra Wolf, Christian Gieger, Joel Schwartz, Pantel S. Vokonas, Lifang Hou, Allan C. Just, Stefania Bandinelli, Dena G. Hernandez, Andrew B. Singleton, Holger Prokisch, Thomas Meitinger, Gabi Kastenmüller, Luigi Ferrucci, Andrea A. Baccarelli, Melanie Waldenberger, Annette Peters
Institutions: Helmholtz Munich, Columbia University, National Institutes of Health, National Institute on Aging, Institut für Humangenetik, Harvard University, Boston University, VA Boston Healthcare System, Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Icahn School of Medicine at Mount Sinai, Azienda Sanitaria di Firenze, Technical University of Munich, German Centre for Cardiovascular Research, Institute of Bioinformatics and Systems Biology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: U.S. Department of Veterans Affairs, European Commission, Bundesministerium für Bildung und Forschung, Ministero della Salute, National Institutes of Health, Helmholtz Zentrum München, National Institute on Aging, National Institute of Environmental Health Sciences, National Institute on Minority Health and Health Disparities
Awards: G1248102086, G1789381357, G2495888254, G2857511458, Prenatal Exposure to Endocrine Disrupters, DNA Methylation, and Childhood Obesity, G2973790809, G3207356259, G3362311673, G374919288, G393177772, G4507648799, G4652745033, G5702163051, G6388590635, Systems Biology to Identify Molecular Targets for Vascular Disease Treatment, G7333524540, ReliabilitY of opto-Transceivers for Health Monitoring Systems, G866381394, HISPANIC SECONDARY STROKE PREVENTION INITIATIVE, Mount Sinai Center for Health and Environment Across the LifeSpan (HEALS)
OpenAlex ID: W2905727269