Genome-wide DNA methylation variability in adolescent monozygotic twins followed since birth

Lévesque, Mélissa L.; Casey, Kevin F.; Szyf, Moshe; Ismaylova, Elmira; Ly, Victoria; Verner, Marie-Pier; Suderman, Matthew; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette; Boivin, Michel; Tremblay, Richard E.; Booij, Linda

doi:10.4161/15592294.2014.970060

Cited by 62 publications

(45 citation statements)

References 67 publications

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“…Significant variation in the neonatal methylome occurs during early development and with changes in the intrauterine environment Levesque et al, 2014;Martino et al, 2013). Therefore, a number of studies have focused on birth weight associated methylation changes in candidate imprinted genes in both newborns and adults, and found associations in the H19 and IGF2 genes (Heijmans et al, 2008;Hoyo et al, 2012;Murphy et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

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DNA Methylation Changes in theIGF1RGene in Birth Weight Discordant Adult Monozygotic Twins

et al. 2015

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Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to predisposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10 −8 ), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (randomeffects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects.

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Section: Discussionmentioning

confidence: 99%

“…The age at DNA extraction was taken into account as a covariate since methylation levels can change over time (Levesque et al, 2014;Martino et al, 2013). Additional covariates, such as smoking status and alcohol consumption, were collected by self-reported questionnaires.…”

Section: Methodsmentioning

confidence: 99%

DNA Methylation Changes in theIGF1RGene in Birth Weight Discordant Adult Monozygotic Twins

et al. 2015

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“…This variation has significant consequences for biological function, health and longevity, and it is important to understand its origin and the factors that determine it. The importance of both genetics and environment can be most clearly seen in studies in twins where monozygotic twins are epigenetically very similar during the early years of life, but differences begin to develop in childhood and accumulate over time, with the magnitude of these being dependent on age and discordance in lifestyle [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 97%

Genetic and metabolic determinants of human epigenetic variation

Haggarty

2015

Current Opinion in Clinical Nutrition and Metabolic Care

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Epigenetics is at the heart of a series of feedback loops linking the environment to the human genome in a way that allows crosstalk between the genome and the environment it exists within. It offers the potential for modification of adverse epigenetic states resulting from events/exposures at earlier life stages. We need to better understand the nutritional programming of epigenetic states, the persistence of these marks in time and their effect on biological function and health in current and future generations.

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“…Our research group previously studied DNA methylation variation as assessed in saliva in a sample of 15-year-old MZ twins in adolescence (Levesque et al, 2014). We assessed genome-wide DNA methylation using the Infinium HumanMethylation450 BeadChip in a sample of 37 MZ twin pairs.…”

Section: Assessing Stability Throughout the Lifespanmentioning

confidence: 99%

Impact of Early Environment on Children's Mental Health: Lessons From DNA Methylation Studies With Monozygotic Twins

et al. 2015

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Over the past decade, epigenetic analyses have made important contributions to our understanding of healthy development and a wide variety of adverse conditions such as cancer and psychopathology. There is increasing evidence that DNA methylation is a mechanism by which environmental factors influence gene transcription and, ultimately, phenotype. However, differentiating the effects of the environment from those of genetics on DNA methylation profiles remains a significant challenge. Monozygotic (MZ) twin study designs are unique in their ability to control for genetic differences because each pair of MZ twins shares essentially the same genetic sequence with the exception of a small number of de novo mutations and copy number variations. Thus, differences within twin pairs in gene expression and phenotype, including behavior, can be attributed in the majority of cases to environmental effects rather than genetic influence. In this article, we review the literature showing how MZ twin designs can be used to study basic epigenetic principles, contributing to understanding the role of early in utero and postnatal environmental factors on the development of psychopathology. We also highlight the importance of initiating longitudinal and experimental studies with MZ twins during pregnancy. This approach is especially important to identify: (1) critical time periods during which the early environment can impact brain and mental health development, and (2) the specific mechanisms through which early environmental effects may be mediated. These studies may inform the optimum timing and design for early preventive interventions aimed at reducing risk for psychopathology.

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Genome-wide DNA methylation variability in adolescent monozygotic twins followed since birth

Cited by 62 publications

References 67 publications

DNA Methylation Changes in theIGF1RGene in Birth Weight Discordant Adult Monozygotic Twins

DNA Methylation Changes in theIGF1RGene in Birth Weight Discordant Adult Monozygotic Twins

Genetic and metabolic determinants of human epigenetic variation

Impact of Early Environment on Children's Mental Health: Lessons From DNA Methylation Studies With Monozygotic Twins

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