DNA methylation biomarkers of myocardial infarction and cardiovascular disease

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• dc.contributor.author Fernández Sanlés, Alba, 1988-
• dc.contributor.author Sayols Baixeras, Sergi, 1988-
• dc.contributor.author Subirana Cachinero, Isaac
• dc.contributor.author Sentí Clapés, Mariano
• dc.contributor.author Pérez-Fernández, Silvia
• dc.contributor.author Castro de Moura, Manuel
• dc.contributor.author Esteller, Manel
• dc.contributor.author Marrugat de la Iglesia, Jaume
• dc.contributor.author Elosua Llanos, Roberto
• dc.date.accessioned 2021-09-08T06:21:10Z
• dc.date.available 2021-09-08T06:21:10Z
• dc.date.issued 2021
• dc.description.abstract Background: The epigenetic landscape underlying cardiovascular disease (CVD) is not completely understood and the clinical value of the identified biomarkers is still limited. We aimed to identify differentially methylated loci associated with acute myocardial infarction (AMI) and assess their validity as predictive and causal biomarkers. Results: We designed a case-control, two-stage, epigenome-wide association study on AMI (ndiscovery = 391, nvalidation = 204). DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. We performed a fixed-effects meta-analysis of the two samples. 34 CpGs were associated with AMI. Only 12 of them were available in two independent cohort studies (n ~ 1800 and n ~ 2500) with incident coronary and cardiovascular disease (CHD and CVD, respectively). The Infinium HumanMethylation450 BeadChip was used in those two studies. Four of the 12 CpGs were validated in association with incident CHD: AHRR-mapping cg05575921, PTCD2-mapping cg25769469, intergenic cg21566642 and MPO-mapping cg04988978. We then assessed whether methylation risk scores based on those CpGs improved the predictive capacity of the Framingham risk function, but they did not. Finally, we aimed to study the causality of those associations using a Mendelian randomization approach but only one of the CpGs had a genetic influence and therefore the results were not conclusive. Conclusions: We have identified 34 CpGs related to AMI. These loci highlight the relevance of smoking, lipid metabolism, and inflammation in the biological mechanisms related to AMI. Four were additionally associated with incident CHD and CVD but did not provide additional predictive information.
• dc.format.mimetype application/pdf
• dc.identifier.citation Fernández-Sanlés A, Sayols-Baixeras S, Subirana I, Sentí M, Pérez-Fernández S, de Castro Moura M, Esteller M, Marrugat J, Elosua R. DNA methylation biomarkers of myocardial infarction and cardiovascular disease. Clin Epigenetics. 2021;13(1):86. DOI: 10.1186/s13148-021-01078-6
• dc.identifier.doi http://dx.doi.org/10.1186/s13148-021-01078-6
• dc.identifier.issn 1868-7075
• dc.identifier.uri http://hdl.handle.net/10230/48409
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof Clin Epigenetics. 2021;13(1):86
• dc.rights © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Cardiovascular disease
• dc.subject.keyword DNA methylation
• dc.subject.keyword Epigenome-wide association study
• dc.subject.keyword Myocardial infarction
• dc.subject.keyword Predictive biomarkers
• dc.title DNA methylation biomarkers of myocardial infarction and cardiovascular disease
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion