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Concordant and discordant DNA methylation signatures of aging in human blood and brain

BACKGROUND: DNA methylation is an epigenetic mark that balances plasticity with stability. While DNA methylation exhibits tissue specificity, it can also vary with age and potentially environmental exposures. In studies of DNA methylation, samples from specific tissues, especially brain, are frequen...

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Autores principales: Farré, Pau, Jones, Meaghan J, Meaney, Michael J, Emberly, Eldon, Turecki, Gustavo, Kobor, Michael S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430927/
https://www.ncbi.nlm.nih.gov/pubmed/25977707
http://dx.doi.org/10.1186/s13072-015-0011-y
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author Farré, Pau
Jones, Meaghan J
Meaney, Michael J
Emberly, Eldon
Turecki, Gustavo
Kobor, Michael S
author_facet Farré, Pau
Jones, Meaghan J
Meaney, Michael J
Emberly, Eldon
Turecki, Gustavo
Kobor, Michael S
author_sort Farré, Pau
collection PubMed
description BACKGROUND: DNA methylation is an epigenetic mark that balances plasticity with stability. While DNA methylation exhibits tissue specificity, it can also vary with age and potentially environmental exposures. In studies of DNA methylation, samples from specific tissues, especially brain, are frequently limited and so surrogate tissues are often used. As yet, we do not fully understand how DNA methylation profiles of these surrogate tissues relate to the profiles of the central tissue of interest. RESULTS: We have adapted principal component analysis to analyze data from the Illumina 450K Human Methylation array using a set of 17 individuals with 3 brain regions and whole blood. All of the top five principal components in our analysis were associated with a variable of interest: principal component 1 (PC1) differentiated brain from blood, PCs 2 and 3 were representative of tissue composition within brain and blood, respectively, and PCs 4 and 5 were associated with age of the individual (PC4 in brain and PC5 in both brain and blood). We validated our age-related PCs in four independent sample sets, including additional brain and blood samples and liver and buccal cells. Gene ontology analysis of all five PCs showed enrichment for processes that inform on the functions of each PC. CONCLUSIONS: Principal component analysis (PCA) allows simultaneous and independent analysis of tissue composition and other phenotypes of interest. We discovered an epigenetic signature of age that is not associated with cell type composition and required no correction for cellular heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-015-0011-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-44309272015-05-15 Concordant and discordant DNA methylation signatures of aging in human blood and brain Farré, Pau Jones, Meaghan J Meaney, Michael J Emberly, Eldon Turecki, Gustavo Kobor, Michael S Epigenetics Chromatin Research BACKGROUND: DNA methylation is an epigenetic mark that balances plasticity with stability. While DNA methylation exhibits tissue specificity, it can also vary with age and potentially environmental exposures. In studies of DNA methylation, samples from specific tissues, especially brain, are frequently limited and so surrogate tissues are often used. As yet, we do not fully understand how DNA methylation profiles of these surrogate tissues relate to the profiles of the central tissue of interest. RESULTS: We have adapted principal component analysis to analyze data from the Illumina 450K Human Methylation array using a set of 17 individuals with 3 brain regions and whole blood. All of the top five principal components in our analysis were associated with a variable of interest: principal component 1 (PC1) differentiated brain from blood, PCs 2 and 3 were representative of tissue composition within brain and blood, respectively, and PCs 4 and 5 were associated with age of the individual (PC4 in brain and PC5 in both brain and blood). We validated our age-related PCs in four independent sample sets, including additional brain and blood samples and liver and buccal cells. Gene ontology analysis of all five PCs showed enrichment for processes that inform on the functions of each PC. CONCLUSIONS: Principal component analysis (PCA) allows simultaneous and independent analysis of tissue composition and other phenotypes of interest. We discovered an epigenetic signature of age that is not associated with cell type composition and required no correction for cellular heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-015-0011-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-09 /pmc/articles/PMC4430927/ /pubmed/25977707 http://dx.doi.org/10.1186/s13072-015-0011-y Text en © Farré et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
Farré, Pau
Jones, Meaghan J
Meaney, Michael J
Emberly, Eldon
Turecki, Gustavo
Kobor, Michael S
Concordant and discordant DNA methylation signatures of aging in human blood and brain
title Concordant and discordant DNA methylation signatures of aging in human blood and brain
title_full Concordant and discordant DNA methylation signatures of aging in human blood and brain
title_fullStr Concordant and discordant DNA methylation signatures of aging in human blood and brain
title_full_unstemmed Concordant and discordant DNA methylation signatures of aging in human blood and brain
title_short Concordant and discordant DNA methylation signatures of aging in human blood and brain
title_sort concordant and discordant dna methylation signatures of aging in human blood and brain
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430927/
https://www.ncbi.nlm.nih.gov/pubmed/25977707
http://dx.doi.org/10.1186/s13072-015-0011-y
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