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
Hlavní autoři: 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.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 07.04.2016
Nature Publishing Group
Nature Portfolio
Témata:
631/208/212/177
631/337/176/1988
Adolescent
Adult
Age
Age Factors
Aging - genetics
Blood
Child, Preschool
CpG Islands
Deoxyribonucleic acid
Disease
DNA
DNA Methylation
Environmental effects
Epidemiology
Epigenetics
Female
Gender differences
Gene-Environment Interaction
Genetic diversity
Genome, Human
Genomes
Humanities and Social Sciences
Humans
Inheritance Patterns
Leukocytes
Male
Metabolism
Metabolites
multidisciplinary
Phenotype
Polymorphism, Single Nucleotide
Science
Science (multidisciplinary)
Sex Factors
Smoking - physiopathology
Twins
Twins, Dizygotic - genetics
Twins, Monozygotic - genetics
Netherlands
ISSN:2041-1723, 2041-1723
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Popis
Shrnutí: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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These authors contributed equally to this work.
These authors jointly supervised this work.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms11115