Birth weight discordance, DNA methylation, and cortical morphology of adolescent monozygotic twins

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

doi:10.1002/hbm.23503

Cited by 28 publications

(27 citation statements)

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“…We and others have previously found in MZ twin pairs that overall brain volume and cortical surface area were positively associated with BW discordance in frontal and temporal brain regions in adolescents and adults (Casey et al, 2017;Levesque et al, 2015;Raznahan, Greenstein, Lee, Clasen, & Giedd, 2012). In the present study, we investigated in MZ adolescent twins recruited from a longitudinal cohort and followed since birth whether differences in the prenatal environment were associated with withinpair differences in rs-FC within the limbic network and DMN.…”

Section: Introductionmentioning

confidence: 84%

“…The twins also performed an implicit emotional processing task, where they were asked to identify the sex of different faces that varied on emotionality (15 min; not discussed here). Portions of the structural and task-based functional connectivity data have been published (Casey et al, 2017;Ismaylova, Levesque, et al, 2018;Levesque et al, 2015). The default CONN denoising steps were applied, including the CompCor strategy which first extracts the five main components from the white matter and CSF signal and regresses them out from the signal.…”

Section: Participantsmentioning

confidence: 99%

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Birth weight is associated with adolescent brain development: A multimodal imaging study in monozygotic twins

Hayward

Pomares

Casey

et al. 2020

Human Brain Mapping

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Previous research has shown that the prenatal environment, commonly indexed by birth weight (BW), is a predictor of morphological brain development. We previously showed in monozygotic (MZ) twins associations between BW and brain morphology that were independent of genetics. In the present study, we employed a longitudinal MZ twin design to investigate whether variations in prenatal environment (as indexed by discordance in BW) are associated with resting-state functional connectivity (rs-FC) and with structural connectivity. We focused on the limbic and default mode networks (DMNs), which are key regions for emotion regulation and internally generated thoughts, respectively. One hundred and six healthy adolescent MZ twins (53 pairs; 42% male pairs) followed longitudinally from birth underwent a magnetic resonance imaging session at age 15. Graph theoretical analysis was applied to rs-FC measures. TrackVis was used to determine track count as an indicator of structural connectivity strength. Lower BW twins had less efficient limbic network connectivity as compared to their higher BW co-twin, driven by differences in the efficiency of the right hippocampus and right amygdala. Lower BW male twins had fewer tracks

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Section: Introductionmentioning

confidence: 84%

Section: Participantsmentioning

confidence: 99%

Birth weight is associated with adolescent brain development: A multimodal imaging study in monozygotic twins

Hayward

Pomares

Casey

et al. 2020

Human Brain Mapping

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“…All twin studies examined birth-weight discordance [ 68 – 76 ]. There were no genome-wide DNAm differences between birth weight-discordant monozygotic (MZ) twins in blood from adults in two papers [ 68 , 69 ], or using saliva samples from 15 year olds in another [ 71 ]. In twin participants aged 22–45 years, although 45 differentially methylated CpGs were identified using saliva samples, there was no difference in the methylation of repetitive elements [ 75 ].…”

Section: Resultsmentioning

confidence: 99%

Associations between body size, nutrition and socioeconomic position in early life and the epigenome: A systematic review

et al. 2018

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BackgroundBody size, nutrition and socioeconomic position (SEP) in early life have been associated with a wide range of long-term health effects. Epigenetics is one possible mechanism through which these early life exposures can impact later life health. We conducted a systematic review examining the observational evidence for the impact of body size, nutrition and SEP in early life on the epigenome in humans.MethodsThis systematic review is registered with the PROSPERO database (registration number: CRD42016050193). Three datasets were simultaneously searched using Ovid and the resulting studies were evaluated by at least two independent reviewers. Studies measuring epigenetic markers either at the same time as, or after, the early life exposure and have a measure of body size, nutrition or SEP in early life (up to 12 years), written in English and from a community-dwelling participants were included.ResultsWe identified 90 eligible studies. Seventeen of these papers examined more than one early life exposure of interest. Fifty six papers examined body size, 37 nutrition and 17 SEP. All of the included papers examined DNA methylation (DNAm) as the epigenetic marker. Overall there was no strong evidence for a consistent association between these early life variables in DNAm which may be due to the heterogeneous study designs, data collection methods and statistical analyses.ConclusionsDespite these inconclusive results, the hypothesis that the early life environment can impact DNAm, potentially persisting into adult life, was supported by some studies and warrants further investigation. We provide recommendations for future studies.

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“…Voxel-wise sad minus neutral and fear minus neutral contrasts were generated at the first level. We calculated within-pair discordance by subtracting the activation contrast of the twin with higher SLC6A4 methylation levels from the activation contrast of the co-twin with lower SLC6A4 methylation levels 29 . Discordance values were then used in the regression analyses, by regressing discordance in brain activation in response to sadness>neutral and fear>neutral independently onto discordance in methylation.…”

Section: Methodsmentioning

confidence: 99%

Serotonin transporter promoter methylation in peripheral cells and neural responses to negative stimuli: A study of adolescent monozygotic twins

et al. 2018

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Several studies have examined associations between peripheral DNA methylation patterns of the serotonin transporter gene (SLC6A4) promoter and symptoms of depression and anxiety. The SLC6A4 promoter methylation has also been associated with frontal-limbic brain responses to negative stimuli. However, it is unclear how much of this association is confounded by DNA sequence variations. We utilized a monozygotic-twin within-pair discordance design, to test whether DNA methylation at specific CpG sites in the SLC6A4 promoter of peripheral cells is associated with greater frontal-limbic brain responses to negative stimuli (sadness and fear), independently of DNA sequence effects. In total 48 pairs of healthy 15-year-old monozygotic twins from the Quebec Newborn Twin Study, followed regularly since birth, underwent functional magnetic resonance imaging while conducting an emotion-processing task. The SLC6A4 promoter methylation level was assessed in saliva samples using pyrosequencing. Relative to the co-twins with lower SLC6A4 promoter methylation levels, twins with higher peripheral SLC6A4 methylation levels showed greater orbitofrontal cortical (OFC) activity and left amygdala-anterior cingulate cortex (ACC) and left amygdala-right OFC connectivity in response to sadness as well as greater ACC-left amygdala and ACC-left insula connectivity in response to fearful stimuli. By utilising a monozygotic-twin design, we provided evidence that associations between peripheral SLC6A4 promoter methylation and frontal-limbic brain responses to negative stimuli are, in part, independent of DNA sequence variations. Although causality cannot be determined here, SLC6A4 promoter methylation may be one of the mechanisms underlying how environmental factors influence the serotonin system, potentially affecting emotional processing through frontal-limbic areas.

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Birth weight discordance, DNA methylation, and cortical morphology of adolescent monozygotic twins

Abstract: The association between BW and cortical morphology in adolescence appears to be attributable to in utero environmental effects, and DNA methylation may play a role in mediating this relationship. Hum Brain Mapp 38:2037-2050, 2017. © 2017 Wiley Periodicals, Inc.

Cited by 28 publications

References 74 publications

Birth weight is associated with adolescent brain development: A multimodal imaging study in monozygotic twins

Birth weight is associated with adolescent brain development: A multimodal imaging study in monozygotic twins

Associations between body size, nutrition and socioeconomic position in early life and the epigenome: A systematic review

Serotonin transporter promoter methylation in peripheral cells and neural responses to negative stimuli: A study of adolescent monozygotic twins

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