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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| Vydáno v: | Nature communications Ročník 7; číslo 1; s. 11115 - 13 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
London
Nature Publishing Group UK
07.04.2016
Nature Publishing Group Nature Portfolio |
| Témata: | |
| ISSN: | 2041-1723, 2041-1723 |
| On-line přístup: | Získat plný text |
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| Abstract | 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.
Differential impact of genetic and environmental influences on DNA methylation may result in sex- and age-related physiological variation and disease susceptibility. By analysing DNA methylome of 2,603 individuals from twin families, here, the authors establish a catalogue of between-individual variation in DNA methylation. |
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| AbstractList | 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. 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.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. Differential impact of genetic and environmental influences on DNA methylation may result in sex- and age-related physiological variation and disease susceptibility. By analysing DNA methylome of 2,603 individuals from twin families, here, the authors establish a catalogue of between-individual variation in DNA methylation. 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. Differential impact of genetic and environmental influences on DNA methylation may result in sex- and age-related physiological variation and disease susceptibility. By analysing DNA methylome of 2,603 individuals from twin families, here, the authors establish a catalogue of between-individual variation in DNA methylation. |
| ArticleNumber | 11115 |
| Author | Ehli, Erik A. van Dongen, Jenny Willemsen, Gonneke Hottenga, Jouke-Jan Jansen, Rick Davies, Gareth E. Beck, Stephan Slagboom, P. Eline Boomsma, Dorret I. Dolan, Conor V. van Iterson, Maarten Suchiman, H. Eka Helmer, Quinta Breeze, Charles E. Heijmans, Bastiaan T. Nivard, Michel G. van Meurs, Joyce B. |
| Author_xml | – sequence: 1 givenname: Jenny surname: van Dongen fullname: van Dongen, Jenny email: j.van.dongen@vu.nl organization: Department of Biological Psychology, VU Amsterdam – sequence: 2 givenname: Michel G. surname: Nivard fullname: Nivard, Michel G. organization: Department of Biological Psychology, VU Amsterdam – sequence: 3 givenname: Gonneke surname: Willemsen fullname: Willemsen, Gonneke organization: Department of Biological Psychology, VU Amsterdam – sequence: 4 givenname: Jouke-Jan surname: Hottenga fullname: Hottenga, Jouke-Jan organization: Department of Biological Psychology, VU Amsterdam – sequence: 5 givenname: Quinta surname: Helmer fullname: Helmer, Quinta organization: Department of Biological Psychology, VU Amsterdam – sequence: 6 givenname: Conor V. surname: Dolan fullname: Dolan, Conor V. organization: Department of Biological Psychology, VU Amsterdam – sequence: 7 givenname: Erik A. surname: Ehli fullname: Ehli, Erik A. organization: Avera Institute for Human Genetics – sequence: 8 givenname: Gareth E. surname: Davies fullname: Davies, Gareth E. organization: Avera Institute for Human Genetics – sequence: 9 givenname: Maarten surname: van Iterson fullname: van Iterson, Maarten organization: Department of Molecular Epidemiology, Leiden University Medical Center – sequence: 10 givenname: Charles E. surname: Breeze fullname: Breeze, Charles E. organization: UCL Cancer Institute, University College London – sequence: 11 givenname: Stephan surname: Beck fullname: Beck, Stephan organization: UCL Cancer Institute, University College London – sequence: 13 givenname: H. Eka surname: Suchiman fullname: Suchiman, H. Eka organization: Department of Molecular Epidemiology, Leiden University Medical Center – sequence: 14 givenname: Rick surname: Jansen fullname: Jansen, Rick organization: Department of Psychiatry, VU University Medical Center – sequence: 15 givenname: Joyce B. surname: van Meurs fullname: van Meurs, Joyce B. organization: Department of Internal Medicine, Erasmus Medical Center – sequence: 16 givenname: Bastiaan T. surname: Heijmans fullname: Heijmans, Bastiaan T. organization: Department of Molecular Epidemiology, Leiden University Medical Center – sequence: 17 givenname: P. Eline surname: Slagboom fullname: Slagboom, P. Eline organization: Department of Molecular Epidemiology, Leiden University Medical Center – sequence: 18 givenname: Dorret I. surname: Boomsma fullname: Boomsma, Dorret I. organization: Department of Biological Psychology, VU Amsterdam |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27051996$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Contributor | Wijmenga, Cisca Veldink, Jan H van der Kallen, Carla J H Uitterlinden, André G Franke, Lude Moed, Matthijs van der Breggen, Ruud Nooren, Irene Tigchelaar, Ettje F Zhernakova, Dasha V van Dijk, Freerk Zhernakova, Sasha Kielbasa, Szymon M t Hoen, Peter A C Stehouwer, Coen D A Bonder, Marc Jan van den Berg, Leonard H van Heemst, Diana Deelen, Joris Verbiest, Michael Luijk, René Pool, René Lakenberg, Nico Van't Hof, Peter Swertz, Morris A van Duijn, Cornelia M Hofman, Bert A Mei, Hailiang van Greevenbroek, Marleen M J van Galen, Michiel Vermaat, Martijn Isaacs, Aaron Bot, Jan Deelen, Patrick Jhamai, P Mila Beekman, Marian Schalkwijk, Casper G Verkerk, Marijn Arindrarto, Wibowo van Rooij, Jeroen van Zwet, Erik W |
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| Copyright | The Author(s) 2016 Copyright Nature Publishing Group Apr 2016 Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. |
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| Title | Genetic and environmental influences interact with age and sex in shaping the human methylome |
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