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A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study

A number of studies have examined the relationship of indices of epigenetic aging (EA) to key health outcomes. Unfortunately, our understanding of the relationship of EA to mortality and substance use-related health variables is unclear. In order to clarify these interpretations, we analyzed the rel...

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Autores principales: Mills, James A., Beach, Steven R.H., Dogan, Meeshanthini, Simons, Ron L., Gibbons, Frederick X., Long, Jeffrey D., Philibert, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356614/
https://www.ncbi.nlm.nih.gov/pubmed/30650672
http://dx.doi.org/10.3390/genes10010051
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author Mills, James A.
Beach, Steven R.H.
Dogan, Meeshanthini
Simons, Ron L.
Gibbons, Frederick X.
Long, Jeffrey D.
Philibert, Robert
author_facet Mills, James A.
Beach, Steven R.H.
Dogan, Meeshanthini
Simons, Ron L.
Gibbons, Frederick X.
Long, Jeffrey D.
Philibert, Robert
author_sort Mills, James A.
collection PubMed
description A number of studies have examined the relationship of indices of epigenetic aging (EA) to key health outcomes. Unfortunately, our understanding of the relationship of EA to mortality and substance use-related health variables is unclear. In order to clarify these interpretations, we analyzed the relationship of the Levine EA index (LEA), as well as established epigenetic indices of cigarette (cg05575921) and alcohol consumption (cg04987734), to all-cause mortality in the Framingham Heart Study Offspring Cohort (n = 2256) Cox proportional hazards regression. We found that cg05575921 and cg04987734 had an independent effect relative to LEA and vice versa, with the model including all the predictors having better performance than models with either LEA or cg05575921 and cg04987734 alone. After correction for multiple comparisons, 195 and 327, respectively, of the 513 markers in the LEA index, as well as the overall index itself, were significantly associated with cg05575921 and cg04987734 methylation status. We conclude that the epigenetic indices of substance use have an independent effect over and above LEA, and are slightly stronger predictors of mortality in head-to-head comparisons. We also conclude that the majority of the strength of association conveyed by the LEA is secondary to smoking and drinking behaviors, and that efforts to promote healthy aging should continue to focus on addressing substance use.
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spelling pubmed-63566142019-02-04 A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study Mills, James A. Beach, Steven R.H. Dogan, Meeshanthini Simons, Ron L. Gibbons, Frederick X. Long, Jeffrey D. Philibert, Robert Genes (Basel) Article A number of studies have examined the relationship of indices of epigenetic aging (EA) to key health outcomes. Unfortunately, our understanding of the relationship of EA to mortality and substance use-related health variables is unclear. In order to clarify these interpretations, we analyzed the relationship of the Levine EA index (LEA), as well as established epigenetic indices of cigarette (cg05575921) and alcohol consumption (cg04987734), to all-cause mortality in the Framingham Heart Study Offspring Cohort (n = 2256) Cox proportional hazards regression. We found that cg05575921 and cg04987734 had an independent effect relative to LEA and vice versa, with the model including all the predictors having better performance than models with either LEA or cg05575921 and cg04987734 alone. After correction for multiple comparisons, 195 and 327, respectively, of the 513 markers in the LEA index, as well as the overall index itself, were significantly associated with cg05575921 and cg04987734 methylation status. We conclude that the epigenetic indices of substance use have an independent effect over and above LEA, and are slightly stronger predictors of mortality in head-to-head comparisons. We also conclude that the majority of the strength of association conveyed by the LEA is secondary to smoking and drinking behaviors, and that efforts to promote healthy aging should continue to focus on addressing substance use. MDPI 2019-01-15 /pmc/articles/PMC6356614/ /pubmed/30650672 http://dx.doi.org/10.3390/genes10010051 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mills, James A.
Beach, Steven R.H.
Dogan, Meeshanthini
Simons, Ron L.
Gibbons, Frederick X.
Long, Jeffrey D.
Philibert, Robert
A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study
title A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study
title_full A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study
title_fullStr A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study
title_full_unstemmed A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study
title_short A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study
title_sort direct comparison of the relationship of epigenetic aging and epigenetic substance consumption markers to mortality in the framingham heart study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356614/
https://www.ncbi.nlm.nih.gov/pubmed/30650672
http://dx.doi.org/10.3390/genes10010051
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