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

BIOS Consortium; Marleen van Greevenbroek; Coen Stehouwer; C.J.H. van der Kallen; Casper Schalkwijk

doi:10.1038/ncomms11115

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

BIOS Consortium, Marleen van Greevenbroek, Coen Stehouwer, C.J.H. van der Kallen, Casper Schalkwijk

Research output: Contribution to journal › Article › Academic › peer-review

179 Citations (Web of Science)

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.

Original language	English
Article number	11115
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11115
Publication status	Published - Apr 2016

Access to Document

10.1038/ncomms11115

Cite this

@article{11c9152434dd444984a5dd1f3ff96ecb,

title = "Genetic and environmental influences interact with age and sex in shaping the human methylome",

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.",

author = "{van Dongen}, Jenny and Nivard, {Michel G.} and Gonneke Willemsen and Jouke-Jan Hottenga and Quinta Helmer and Dolan, {Conor V.} and Ehli, {Erik A.} and Davies, {Gareth E.} and {van Iterson}, Maarten and Breeze, {Charles E.} and Stephan Beck and Suchiman, {H. Eka} and Rick Jansen and {van Meurs}, {Joyce B. J.} and Heijmans, {Bastiaan T.} and Slagboom, {P. Eline} and {BIOS Consortium} and {van Greevenbroek}, Marleen and Coen Stehouwer and {van der Kallen}, C.J.H. and Casper Schalkwijk and Boomsma, {Dorret I.}",

year = "2016",

month = apr,

doi = "10.1038/ncomms11115",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Genetic and environmental influences interact with age and sex in shaping the human methylome

AU - van Dongen, Jenny

AU - Nivard, Michel G.

AU - Willemsen, Gonneke

AU - Hottenga, Jouke-Jan

AU - Helmer, Quinta

AU - Dolan, Conor V.

AU - Ehli, Erik A.

AU - Davies, Gareth E.

AU - van Iterson, Maarten

AU - Breeze, Charles E.

AU - Beck, Stephan

AU - Suchiman, H. Eka

AU - Jansen, Rick

AU - van Meurs, Joyce B. J.

AU - Heijmans, Bastiaan T.

AU - Slagboom, P. Eline

AU - BIOS Consortium

AU - van Greevenbroek, Marleen

AU - Stehouwer, Coen

AU - van der Kallen, C.J.H.

AU - Schalkwijk, Casper

AU - Boomsma, Dorret I.

PY - 2016/4

Y1 - 2016/4

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms11115

DO - 10.1038/ncomms11115

M3 - Article

C2 - 27051996

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 11115

ER -