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.
authors.affiliation: Department of Biological Psychology, VU Amsterdam, Van der Boechorststraat 1, 1081BT Amsterdam, The Netherlands.
authors.forename: Jenny
authors.initials: J
authors.lastname: van Dongen
authors.affiliation: Department of Biological Psychology, VU Amsterdam, Van der Boechorststraat 1, 1081BT Amsterdam, The Netherlands.
authors.forename: Michel G
authors.initials: MG
authors.lastname: Nivard
authors.affiliation: Department of Biological Psychology, VU Amsterdam, Van der Boechorststraat 1, 1081BT Amsterdam, The Netherlands.
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: Department of Biological Psychology, VU Amsterdam, Van der Boechorststraat 1, 1081BT Amsterdam, The Netherlands.
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.affiliation: Department of Biological Psychology, VU Amsterdam, Van der Boechorststraat 1, 1081BT Amsterdam, The Netherlands.
authors.forename: Quinta
authors.initials: Q
authors.lastname: Helmer
authors.affiliation: Department of Biological Psychology, VU Amsterdam, Van der Boechorststraat 1, 1081BT Amsterdam, The Netherlands.
authors.forename: Conor V
authors.initials: CV
authors.lastname: Dolan
authors.affiliation: Avera Institute for Human Genetics, 3720 W. 69th Street, Sioux Falls, South Dakota 57108, USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Ehli
authors.affiliation: Avera Institute for Human Genetics, 3720 W. 69th Street, Sioux Falls, South Dakota 57108, USA.
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Davies
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Postzone S5-P, Postbus 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van Iterson
authors.affiliation: UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Breeze
authors.affiliation: UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK.
authors.forename: Stephan
authors.initials: S
authors.lastname: Beck
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Postzone S5-P, Postbus 9600, 2300 RC Leiden, The Netherlands.
authors.forename: H Eka
authors.initials: HE
authors.lastname: Suchiman
authors.affiliation: Department of Psychiatry, VU University Medical Center, A.J. Ernststraat 1187, 1081 HL Amsterdam, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Jansen
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Joyce B
authors.initials: JB
authors.lastname: van Meurs
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Postzone S5-P, Postbus 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Bastiaan T
authors.initials: BT
authors.lastname: Heijmans
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Postzone S5-P, Postbus 9600, 2300 RC Leiden, The Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Biological Psychology, VU Amsterdam, Van der Boechorststraat 1, 1081BT Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000375:Aging / Q000235:genetics; D002675:Child, Preschool; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D059647:Gene-Environment Interaction; D015894:Genome, Human; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D012907:Smoking / Q000503:physiopathology; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*