title: Epigenetic variation in monozygotic twins: a genome-wide analysis of DNA methylation in buccal cells.
abstract: DNA methylation is one of the most extensively studied epigenetic marks in humans. Yet, it is largely unknown what causes variation in DNA methylation between individuals. The comparison of DNA methylation profiles of monozygotic (MZ) twins offers a unique experimental design to examine the extent to which such variation is related to individual-specific environmental influences and stochastic events or to familial factors (DNA sequence and shared environment). We measured genome-wide DNA methylation in buccal samples from ten MZ pairs (age 8-19) using the Illumina 450k array and examined twin correlations for methylation level at 420,921 CpGs after QC. After selecting CpGs showing the most variation in the methylation level between subjects, the mean genome-wide correlation (rho) was 0.54. The correlation was higher, on average, for CpGs within CpG islands (CGIs), compared to CGI shores, shelves and non-CGI regions, particularly at hypomethylated CpGs. This finding suggests that individual-specific environmental and stochastic influences account for more variation in DNA methylation in CpG-poor regions. Our findings also indicate that it is worthwhile to examine heritable and shared environmental influences on buccal DNA methylation in larger studies that also include dizygotic twins.
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. j.van.dongen@vu.nl.
authors.forename: Jenny
authors.initials: J
authors.lastname: van Dongen
authors.affiliation: Avera Institute for Human Genetics, 3720 W. 69th Street, Sioux Falls, SD 57108, USA. Erik.Ehli@avera.org.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Ehli
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. R.C.Slieker@lumc.nl.
authors.forename: Roderick C
authors.initials: RC
authors.lastname: Slieker
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. m.bartels@vu.nl.
authors.forename: Meike
authors.initials: M
authors.lastname: Bartels
authors.affiliation: Avera Institute for Human Genetics, 3720 W. 69th Street, Sioux Falls, SD 57108, USA. Zachary.Weber@avera.org.
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Weber
authors.affiliation: Avera Institute for Human Genetics, 3720 W. 69th Street, Sioux Falls, SD 57108, USA. Gareth.Davies@avera.org.
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Davies
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. P.Slagboom@lumc.nl.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. B.T.Heijmans@lumc.nl.
authors.forename: Bastiaan T
authors.initials: BT
authors.lastname: Heijmans
authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. di.boomsma@vu.nl.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma