Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

Abstract

Neonatal molecular biomarkers of neurobehavioral responses (measures of brain-behavior relationships), when combined with neurobehavioral performance measures, could lead to better predictions of long-term developmental outcomes. To this end, we examined whether variability in buccal cell DNA methylation (DNAm) associated with neurobehavioral profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA) and participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study (N = 536). We tested whether epigenetic age, age acceleration, or DNAm levels at individual loci differed between infants based on their NICU Network Neurobehavioral Scale (NNNS) profile classifications. We adjusted for recruitment site, infant sex, PMA, and tissue heterogeneity. Infants with an optimally well-regulated NNNS profile had older epigenetic age compared to other NOVI infants (β 1 = 0.201, p-value = 0.026), but no significant difference in age acceleration. In contrast, infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). Some of the genes annotated to these CpGs included PLA2G4E , TRIM9 , GRIK3 , and MACROD2 , which have previously been associated with neurological structure and function, or with neurobehavioral disorders. These findings contribute to the existing evidence that neonatal epigenetic variations may be informative for infant neurobehavior.

Construction and Validation of a 13-Gene Signature for Prognosis Prediction in Medulloblastoma

“…It was known to regulate synapse formation, synapse elimination (Ou et al, 2010;Park et al, 2011), hippocampal neurons related pathways, and hippocampal long-term potentiation (Cho et al, 2015;Joe et al, 2017). PLA2G4E was reported to be strongly expressed in the brain, especially in neurons (Ogura et al, 2016), and was associated with neurobehavioral disorders (Everson et al, 2019;Morimoto et al, 2018).…”

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

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Environment-driven reprogramming of gamete DNA methylation occurs during maturation and is transmitted intergenerationally in salmon

“…Glutamatergic signalling is an important excitory driver of the hypothalamic-pituitary-adrenal (HPA) axis that, among other functions, mediates organismal stress responses and aggression and it has been hypothesized that selection on these pathways underlies "tameness" in domesticated animals and attenuated stress responses under crowded conditions (O'Rourke and Boeckx 2020). Furthermore, differential methylation of glutamate receptors has been reported in response to prenatal stress in cows (Littlejohn et al 2018) and is associated with adverse behavioural phenotypes in preterm infant humans (Everson et al 2019). This raises the hypothesis that adult SAS fish could transmit information about the crowding they experienced prior to spawning to their offspring in order to prime them for a highly competitive environment upon hatching (Christie et al 2012).…”