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Genetic and environmental influences interact with age and sex in shaping the human methylome

The methylome is subject to genetic and environmental effects. Their impact may depend on sex and age, resulting in sex- and age-related physiological variation and disease susceptibility. Here we estimate the total heritability of DNA methylation levels in whole blood and estimate the variance expl...

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Autores principales: van Dongen, Jenny, Nivard, Michel G., Willemsen, Gonneke, Hottenga, Jouke-Jan, Helmer, Quinta, Dolan, Conor V., Ehli, Erik A., Davies, Gareth E., van Iterson, Maarten, Breeze, Charles E., Beck, Stephan, Suchiman, H. Eka, Jansen, Rick, van Meurs, Joyce B., Heijmans, Bastiaan T., Slagboom, P. Eline, Boomsma, Dorret I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820961/
https://www.ncbi.nlm.nih.gov/pubmed/27051996
http://dx.doi.org/10.1038/ncomms11115
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author van Dongen, Jenny
Nivard, Michel G.
Willemsen, Gonneke
Hottenga, Jouke-Jan
Helmer, Quinta
Dolan, Conor V.
Ehli, Erik A.
Davies, Gareth E.
van Iterson, Maarten
Breeze, Charles E.
Beck, Stephan
Suchiman, H. Eka
Jansen, Rick
van Meurs, Joyce B.
Heijmans, Bastiaan T.
Slagboom, P. Eline
Boomsma, Dorret I.
author_facet van Dongen, Jenny
Nivard, Michel G.
Willemsen, Gonneke
Hottenga, Jouke-Jan
Helmer, Quinta
Dolan, Conor V.
Ehli, Erik A.
Davies, Gareth E.
van Iterson, Maarten
Breeze, Charles E.
Beck, Stephan
Suchiman, H. Eka
Jansen, Rick
van Meurs, Joyce B.
Heijmans, Bastiaan T.
Slagboom, P. Eline
Boomsma, Dorret I.
author_sort van Dongen, Jenny
collection PubMed
description The methylome is subject to genetic and environmental effects. Their impact may depend on sex and age, resulting in sex- and age-related physiological variation and disease susceptibility. Here we estimate the total heritability of DNA methylation levels in whole blood and estimate the variance explained by common single nucleotide polymorphisms at 411,169 sites in 2,603 individuals from twin families, to establish a catalogue of between-individual variation in DNA methylation. Heritability estimates vary across the genome (mean=19%) and interaction analyses reveal thousands of sites with sex-specific heritability as well as sites where the environmental variance increases with age. Integration with previously published data illustrates the impact of genome and environment across the lifespan at methylation sites associated with metabolic traits, smoking and ageing. These findings demonstrate that our catalogue holds valuable information on locations in the genome where methylation variation between people may reflect disease-relevant environmental exposures or genetic variation.
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spelling pubmed-48209612016-04-17 Genetic and environmental influences interact with age and sex in shaping the human methylome van Dongen, Jenny Nivard, Michel G. Willemsen, Gonneke Hottenga, Jouke-Jan Helmer, Quinta Dolan, Conor V. Ehli, Erik A. Davies, Gareth E. van Iterson, Maarten Breeze, Charles E. Beck, Stephan Suchiman, H. Eka Jansen, Rick van Meurs, Joyce B. Heijmans, Bastiaan T. Slagboom, P. Eline Boomsma, Dorret I. Nat Commun Article The methylome is subject to genetic and environmental effects. Their impact may depend on sex and age, resulting in sex- and age-related physiological variation and disease susceptibility. Here we estimate the total heritability of DNA methylation levels in whole blood and estimate the variance explained by common single nucleotide polymorphisms at 411,169 sites in 2,603 individuals from twin families, to establish a catalogue of between-individual variation in DNA methylation. Heritability estimates vary across the genome (mean=19%) and interaction analyses reveal thousands of sites with sex-specific heritability as well as sites where the environmental variance increases with age. Integration with previously published data illustrates the impact of genome and environment across the lifespan at methylation sites associated with metabolic traits, smoking and ageing. These findings demonstrate that our catalogue holds valuable information on locations in the genome where methylation variation between people may reflect disease-relevant environmental exposures or genetic variation. Nature Publishing Group 2016-03-30 /pmc/articles/PMC4820961/ /pubmed/27051996 http://dx.doi.org/10.1038/ncomms11115 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
van Dongen, Jenny
Nivard, Michel G.
Willemsen, Gonneke
Hottenga, Jouke-Jan
Helmer, Quinta
Dolan, Conor V.
Ehli, Erik A.
Davies, Gareth E.
van Iterson, Maarten
Breeze, Charles E.
Beck, Stephan
Suchiman, H. Eka
Jansen, Rick
van Meurs, Joyce B.
Heijmans, Bastiaan T.
Slagboom, P. Eline
Boomsma, Dorret I.
Genetic and environmental influences interact with age and sex in shaping the human methylome
title Genetic and environmental influences interact with age and sex in shaping the human methylome
title_full Genetic and environmental influences interact with age and sex in shaping the human methylome
title_fullStr Genetic and environmental influences interact with age and sex in shaping the human methylome
title_full_unstemmed Genetic and environmental influences interact with age and sex in shaping the human methylome
title_short Genetic and environmental influences interact with age and sex in shaping the human methylome
title_sort genetic and environmental influences interact with age and sex in shaping the human methylome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820961/
https://www.ncbi.nlm.nih.gov/pubmed/27051996
http://dx.doi.org/10.1038/ncomms11115
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