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

BACKGROUND: 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 resu...

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Autores principales: Ward-Caviness, Cavin K., Agha, Golareh, Chen, Brian H., Pfeiffer, Liliane, Wilson, Rory, Wolf, Petra, Gieger, Christian, Schwartz, Joel, Vokonas, Pantel S., Hou, Lifang, Just, Allan C., Bandinelli, Stefania, Hernandez, Dena G., Singleton, Andrew B., Prokisch, Holger, Meitinger, Thomas, Kastenmüller, Gabi, Ferrucci, Luigi, Baccarelli, Andrea A., Waldenberger, Melanie, Peters, Annette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307146/
https://www.ncbi.nlm.nih.gov/pubmed/30587240
http://dx.doi.org/10.1186/s13148-018-0588-7
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author Ward-Caviness, Cavin K.
Agha, Golareh
Chen, Brian H.
Pfeiffer, Liliane
Wilson, Rory
Wolf, Petra
Gieger, Christian
Schwartz, Joel
Vokonas, Pantel S.
Hou, Lifang
Just, Allan C.
Bandinelli, Stefania
Hernandez, Dena G.
Singleton, Andrew B.
Prokisch, Holger
Meitinger, Thomas
Kastenmüller, Gabi
Ferrucci, Luigi
Baccarelli, Andrea A.
Waldenberger, Melanie
Peters, Annette
author_facet Ward-Caviness, Cavin K.
Agha, Golareh
Chen, Brian H.
Pfeiffer, Liliane
Wilson, Rory
Wolf, Petra
Gieger, Christian
Schwartz, Joel
Vokonas, Pantel S.
Hou, Lifang
Just, Allan C.
Bandinelli, Stefania
Hernandez, Dena G.
Singleton, Andrew B.
Prokisch, Holger
Meitinger, Thomas
Kastenmüller, Gabi
Ferrucci, Luigi
Baccarelli, Andrea A.
Waldenberger, Melanie
Peters, Annette
author_sort Ward-Caviness, Cavin K.
collection PubMed
description BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-018-0588-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-63071462019-01-02 Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction Ward-Caviness, Cavin K. Agha, Golareh Chen, Brian H. Pfeiffer, Liliane Wilson, Rory Wolf, Petra Gieger, Christian Schwartz, Joel Vokonas, Pantel S. Hou, Lifang Just, Allan C. Bandinelli, Stefania Hernandez, Dena G. Singleton, Andrew B. Prokisch, Holger Meitinger, Thomas Kastenmüller, Gabi Ferrucci, Luigi Baccarelli, Andrea A. Waldenberger, Melanie Peters, Annette Clin Epigenetics Research BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13148-018-0588-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-27 /pmc/articles/PMC6307146/ /pubmed/30587240 http://dx.doi.org/10.1186/s13148-018-0588-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ward-Caviness, Cavin K.
Agha, Golareh
Chen, Brian H.
Pfeiffer, Liliane
Wilson, Rory
Wolf, Petra
Gieger, Christian
Schwartz, Joel
Vokonas, Pantel S.
Hou, Lifang
Just, Allan C.
Bandinelli, Stefania
Hernandez, Dena G.
Singleton, Andrew B.
Prokisch, Holger
Meitinger, Thomas
Kastenmüller, Gabi
Ferrucci, Luigi
Baccarelli, Andrea A.
Waldenberger, Melanie
Peters, Annette
Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction
title Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction
title_full Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction
title_fullStr Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction
title_full_unstemmed Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction
title_short Analysis of repeated leukocyte DNA methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction
title_sort analysis of repeated leukocyte dna methylation assessments reveals persistent epigenetic alterations after an incident myocardial infarction
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307146/
https://www.ncbi.nlm.nih.gov/pubmed/30587240
http://dx.doi.org/10.1186/s13148-018-0588-7
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