Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for GABBR1

Vangeel, Elise; Pishva, Ehsan; Hompes, Titia; Hove, Daniël L.A. van den; Lambrechts, Diether; Allegaert, Karel; Freson, Kathleen; Izzi, Benedetta; Claes, Stephan

doi:10.1186/s13148-017-0408-5

Cited by 36 publications

(30 citation statements)

References 65 publications

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“…Analysis of DNA extracted from cord blood from neonates demonstrated that gestational age can be reliably predicted between 24 and 44 weeks 10 . These results are consistent with results from induced pluripotent stem cells (iPSCs) that show they are considerably younger than the cells they were derived from 3,11 .…”

Section: Introductionsupporting

confidence: 90%

Synchrony and asynchrony between an epigenetic clock and developmental timing

Hoshino

Horvath

Sridhar

et al. 2019

Sci Rep

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Epigenetic changes have been used to estimate chronological age across the lifespan, and some studies suggest that epigenetic “aging” clocks may already operate in developing tissue. To better understand the relationship between developmental stage and epigenetic age, we utilized the highly regular sequence of development found in the mammalian neural retina and a well-established epigenetic aging clock based on DNA methylation. Our results demonstrate that the epigenetic age of fetal retina is highly correlated with chronological age. We further establish that epigenetic aging progresses normally in vitro , suggesting that epigenetic aging is a property of individual tissues. This correlation is also retained in stem cell-derived retinal organoids, but is accelerated in individuals with Down syndrome, a progeroid-like condition. Overall, our results suggest that epigenetic aging begins as early as a few weeks post-conception, in fetal tissues, and the mechanisms underlying the phenomenon of epigenetic aging might be studied in developing organs.

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Section: Introductionsupporting

confidence: 90%

Synchrony and asynchrony between an epigenetic clock and developmental timing

Hoshino

Horvath

Sridhar

et al. 2019

Sci Rep

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“…But there was no evidence of sexually dimorphic effects of maternal prenatal cortisol in this study [51]. Similarly, Vangeel et al ( N = 45) found an interaction such that prenatal anxiety was positively associated with cord blood DNA methylation in the GABA-B receptor subunit 1 gene ( GABBR1 ) in infant boys but not girls [53]. Mina et al found sex-specific associations suggesting that infant girls might be particularly susceptible to the effects of prenatal maternal distress on placental mRNA levels of genes regulating fetal glucocorticoid exposure and placental growth [68].…”

Section: Resultsmentioning

confidence: 64%

Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature

Sutherland

Brunwasser

2018

Curr Psychiatry Rep

128

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Most articles (k = 35) found evidence of either sex-specific associations (significant in one sex but not the other) or significant PNMSstress interactions for at least one child health outcome. Evidence for sex-dependent effects was strongest in the group of studies evaluating child neural/nervous system development and temperament as outcomes. There is sufficient evidence of sex-dependent associations to recommend that researchers always consider the potential role of child sex in PNMS programming studies and report descriptive statistics for study outcomes stratified by child biological sex.

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“…As there is accumulating evidence for sex differences in DNA methylation changes associated with adverse prenatal exposures [51][52][53][54], we explored differences in the methylation signatures associated with GDM exposure in male versus female infants (Table J in S1 Data). In PLOS MEDICINE…”

Section: Identification Of Dmcpgs In Cord Blood Associated With Matermentioning

confidence: 99%

Maternal dysglycaemia, changes in the infant’s epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial

et al. 2020

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Background Higher maternal plasma glucose (PG) concentrations, even below gestational diabetes mellitus (GDM) thresholds, are associated with adverse offspring outcomes, with DNA methylation proposed as a mediating mechanism. Here, we examined the relationships between maternal dysglycaemia at 24 to 28 weeks’ gestation and DNA methylation in neonates and whether a dietary and physical activity intervention in pregnant women with obesity modified the methylation signatures associated with maternal dysglycaemia. Methods and findings We investigated 557 women, recruited between 2009 and 2014 from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a randomised controlled trial (RCT), of a lifestyle intervention (low glycaemic index (GI) diet plus physical activity) in pregnant women with obesity (294 contol, 263 intervention). Between 27 and 28 weeks of pregnancy, participants had an oral glucose (75 g) tolerance test (OGTT), and GDM diagnosis was based on diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), with 159 women having a diagnosis of GDM. Cord blood DNA samples from the infants were interrogated for genome-wide DNA methylation levels using the Infinium Human MethylationEPIC BeadChip array. Robust regression was carried out, adjusting for maternal age, smoking, parity, ethnicity, neonate sex, and predicted cell-type composition. Maternal GDM, fasting glucose, 1-h, and 2-h glucose concentrations following an OGTT were associated with 242, 1, 592, and 17 differentially methylated cytosine-phosphate-guanine (dmCpG) sites (false discovery rate (FDR) ≤ 0.05), respectively, in the infant’s cord blood DNA. The most significantly GDM-associated CpG was cg03566881 located within the leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) (FDR = 0.0002). Moreover, we show that the GDM and 1-h glucose-associated methylation signatures in the cord blood of the infant appeared to be attenuated by the dietary and physical activity intervention during pregnancy; in the intervention arm, there were no GDM and two 1-h glucose-associated dmCpGs, whereas in the standard care arm, there were 41 GDM and 160 1-h glucose-associated dmCpGs. A total of 87% of the GDM and 77% of the 1-h glucose-associated dmCpGs had smaller effect sizes in the intervention compared to the standard care arm; the adjusted r2 for the association of LGR6 cg03566881 with GDM was 0.317 (95% confidence interval (CI) 0.012, 0.022) in the standard care and 0.240 (95% CI 0.001, 0.015) in the intervention arm. Limitations included measurement of DNA methylation in cord blood, where the functional significance of such changes are unclear, and because of the strong collinearity between treatment modality and severity of hyperglycaemia, we cannot exclude that treatment-related differences are potential confounders. Conclusions Maternal dysglycaemia was associated with significant changes in the epigenome of the infants. Moreover, we found that the epigenetic impact of a dysglycaemic prenatal maternal environment appeared to be modified by a lifestyle intervention in pregnancy. Further research will be needed to investigate possible medical implications of the findings. Trial registration ISRCTN89971375.

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Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for GABBR1

Cited by 36 publications

References 65 publications

Synchrony and asynchrony between an epigenetic clock and developmental timing

Synchrony and asynchrony between an epigenetic clock and developmental timing

Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature

Maternal dysglycaemia, changes in the infant’s epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial

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