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Epigenetic signature of birth weight discordance in adult twins.

ABSTRACT: BACKGROUND: A low birth weight has been extensively related to poor adult health outcomes. Birth weight can be seen as a proxy for environmental conditions during prenatal development. Identical twin pairs discordant for birth weight provide an extraordinary model for investigating the association between birth weight and adult life health while controlling for not only genetics but also postnatal rearing environment. We performed an epigenome-wide profiling on blood samples from 150 pairs of adult monozygotic twins discordant for birth weight to look for molecular evidence of epigenetic signatures in association with birth weight discordance. RESULTS: Our association analysis revealed no CpG site with genome-wide statistical significance (FDR < 0.05) for either qualitative (larger or smaller) or quantitative discordance in birth weight. Even with selected samples of extremely birth weight discordant twin pairs, no significant site was found except for 3 CpGs that displayed age-dependent intra-pair differential methylation with FDRs 0.014 (cg26856578, p = 3.42e-08), 0.0256 (cg15122603, p = 1.25e-07) and 0.0258 (cg16636641, p = 2.05e-07). Among the three sites, intra-pair differential methylation increased with age for cg26856578 but decreased with age for cg15122603 and cg16636641. There was no genome-wide statistical significance for sex-dependent effects on intra-pair differential methylation in either the whole samples or the extremely discordant twins. CONCLUSIONS: Genome-wide DNA methylation profiling did not reveal epigenetic signatures of birth weight discordance although some sites displayed age-dependent intra-pair differential methylation in the extremely discordant twin pairs.

SUBMITTER: Tan Q

PROVIDER: S-EPMC4302120 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Epigenetic signature of birth weight discordance in adult twins.

Tan Qihua Q Frost Morten M Heijmans Bastiaan T BT von Bornemann Hjelmborg Jacob J Tobi Elmar W EW Christensen Kaare K Christiansen Lene L

BMC genomics 20141204

<h4>Background</h4>A low birth weight has been extensively related to poor adult health outcomes. Birth weight can be seen as a proxy for environmental conditions during prenatal development. Identical twin pairs discordant for birth weight provide an extraordinary model for investigating the association between birth weight and adult life health while controlling for not only genetics but also postnatal rearing environment. We performed an epigenome-wide profiling on blood samples from 150 pair ...[more]

PMID: 25476734

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Project description:T cells mediate the inflammatory responses observed in asthma among genetically susceptible individuals and have been suspected to be prone to epigenetic regulation. However, these relationships are not well established from past clinical studies that have had limited capacity to control for the effects of variable genetic predisposition and early environmental exposures. Relying on a cohort of monozygotic twins discordant for asthma we sought to determine if epigenetic modifications in T cells were associated with current asthma and explored whether such modifications were associated with second hand smoke exposures. Our study was conducted in a monozygotic twin cohort of adult twin pairs (n = 21) all discordant for asthma. Regulatory T cell (Treg) and effector T cell (Teff) subsets were assessed for levels of cellular function, protein expression, gene expression and CpG methylation within Forkhead box P3 (FOXP3) and interferon gamma-γ (IFNγ) loci. Comparisons by asthma and current report of exposure to second hand smoke were made. Treg from asthmatic discordant twins demonstrated decreased FOXP3 protein expression and impaired Treg function that was associated with increased levels of CpG methylation within the FOXP3 locus when compared to their non-asthmatic twin partner. In parallel, Teff from discordant asthmatic twins demonstrated increased methylation of the IFNγ locus, decreased IFNγ expression and reduced Teff function when compared to Teff from the non-asthmatic twin. Finally, report of current exposure to second hand smoke was associated with modifications in both Treg and Teff at the transcriptional level among asthmatics. The results of the current study provide evidence for differential function of T cell subsets in monozygotic twins discordant for asthma that are regulated by changes in DNA methylation. Our preliminary data suggest exposure to second hand smoke may augment the modified T cell responses associated with asthma.

Project description:BackgroundBirthweight discordance is well studied, with less known about longitudinal inter-twin differences in foetal growth.ObjectiveTo examine inter-twin per cent differences in EFW (EFW% ), head (HC% ) and abdominal circumference (AC% ), and femur length (FL% ) across gestation in dichorionic twin gestations and explore associated characteristics.MethodsFoetal biometrics were assessed by ultrasound and EFW calculated at ≤6 study visits among women with dichorionic twin pregnancies enrolled in the NICHD Fetal Growth Studies cohort (US, 2012-2013). Inter-twin per cent difference was defined: ([Sizelarger twin - Sizesmaller twin ]/Sizelarger twin × 100). Linear mixed models evaluated per cent differences in foetal biometrics at 15 weeks and their change per week overall and by maternal/neonatal characteristics in unadjusted and adjusted models.ResultsIn 140 pregnancies, inter-twin per cent differences increased across gestation for EFW (0.18%/week, 95% confidence interval [CI] 0.10, 0.27), HC (0.03%/week, 95% CI 0.00, 0.06), and AC (0.03%/week, 95%CI -0.01, 0.08) but decreased for FL (-0.03%/week, 95% CI -0.09, 0.02). After adjustment, change in EFW% difference across gestation differed by pre-pregnancy body mass index (BMI [kg/m2 ]; underweight [<18.5]; normal weight [18.5-24.9]; overweight [25.0-29.9]; obese [≥30.0]; Pinteraction = .022); and conception method (in vitro fertilisation [IVF], intrauterine insemination, ovulation induction medication, donor egg/embryo, none; Pinteraction = .060). While EFW% difference increased with normal pre-pregnancy BMI (0.24%/week, 95% CI 0.12, 0.37), little change was noted with pre-pregnancy obesity (0.01%/week, 95% CI -0.15, 0.17). EFW% difference increased in conceptions without fertility treatments (0.23%/week, 95% CI 0.11, 0.34) but not IVF conceptions (-0.00%/week, 95% CI -0.16, 0.16). Similar patterns of differences across gestation were noted for HC% by conception method (Pinteraction = .026) and AC% by pre-pregnancy BMI (Pinteraction = .071); changes in HC% differed by parity (nulliparous, multiparous; Pinteraction = .004).ConclusionsEFW% difference increased across gestation in dichorionic twins, but remained stable with pre-pregnancy obesity or IVF conception, patterns mirrored for HC and AC. Research is needed to understand pathologic versus physiologic differential twin growth trajectories.

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Epigenetic signature of birth weight discordance in adult twins.

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Epigenetic signature of birth weight discordance in adult twins.

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