title: Genome-wide DNA methylation variability in adolescent monozygotic twins followed since birth.
abstract: DNA methylation patterns are characterized by highly conserved developmental programs, but allow for divergent gene expression resulting from stochastic epigenetic drift or divergent environments. Genome-wide methylation studies in monozygotic (MZ) twins are providing insight into the extent of epigenetic variation that occurs, irrespective of genotype. However, little is known about the variability of DNA methylation patterns in adolescence, a period involving significant and rapid physical, emotional, social, and neurodevelopmental change. Here, we assessed genome-wide DNA methylation using the 450 K Illumina BeadChip in a sample of 37 MZ twin pairs followed longitudinally since birth to investigate: 1) the extent of variation in DNA methylation in identical genetic backgrounds in adolescence and; 2) whether these variations are randomly distributed or enriched in particular functional pathways. We also assessed stability of DNA methylation over 3-6 months to distinguish stable trait-like and variable state-like genes. A pathway analysis found high within-pair variability in genes associated with development, cellular mechanisms, tissue and cell morphology, and various disorders. Test-retest analyses performed in a sub-sample of 8 twin pairs demonstrated enrichment in gene pathways involved in organismal development, cellular growth and proliferation, cell signaling, and particular disorders. The variability found in functional gene pathways may plausibly underlie phenotypic differences in this adolescent MZ twin sample. Furthermore, we assessed stability of methylation over 3-6 months and found that some genes were stable while others were unstable, suggesting that the methylome remains dynamic in adolescence and that dynamic sites tend to be organized in certain gene pathways.
authors.affiliation: a CHU Sainte-Justine Research Center ; Montreal , Canada.
authors.forename: Mélissa L
authors.initials: ML
authors.lastname: Lévesque
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Casey
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
authors.forename: Elmira
authors.initials: E
authors.lastname: Ismaylova
authors.forename: Victoria
authors.initials: V
authors.lastname: Ly
authors.forename: Marie-Pier
authors.initials: MP
authors.lastname: Verner
authors.forename: Matthew
authors.initials: M
authors.lastname: Suderman
authors.forename: Mara
authors.initials: M
authors.lastname: Brendgen
authors.forename: Frank
authors.initials: F
authors.lastname: Vitaro
authors.forename: Ginette
authors.initials: G
authors.lastname: Dionne
authors.forename: Michel
authors.initials: M
authors.lastname: Boivin
authors.forename: Richard E
authors.initials: RE
authors.lastname: Tremblay
authors.forename: Linda
authors.initials: L
authors.lastname: Booij
mesh_terms: D000293:Adolescent; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D013997:Time Factors; D014430:Twins, Monozygotic / Q000235:genetics*
keywords: CBMC, cord blood mononuclear cells; DNA methylation; HLA, human leukocyte antigen; HUVEC, human umbilical vascular endothelial cells; IPA, Ingenuity Pathway Analysis; K-SADS, Kiddie-Schedule for Affective Disorders and Schizophrenia; MHC, major histocompatibility complex; MZ, monozygotic; QNTS, Quebec Newborn Twin Study; environment; epigenetic; monozygotic twins; stability; state-trait; variability; whole-genome