Document Type
Article
Publication Date
4-19-2019
Identifier
DOI: 10.1038/s41598-019-42654-4; PMCID: PMC6474865
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 (β1 = 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.
Journal Title
Sci Rep
Volume
9
Issue
1
First Page
6322
Last Page
6322
MeSH Keywords
Child; CpG Islands; DNA Methylation; Female; Humans; Infant; Infant Behavior; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Nerve Tissue Proteins
Keywords
Child; CpG Islands; DNA Methylation; Female; Humans; Infant; Infant Behavior; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Nerve Tissue Proteins
Recommended Citation
Everson TM, Marsit CJ, Michael O'Shea T, et al. Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants. Sci Rep. 2019;9(1):6322. Published 2019 Apr 19. doi:10.1038/s41598-019-42654-4
Comments
Grant support
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Publisher's Link: https://doi.org/10.1038/s41598-019-42654-4