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

• Type of Material: Article
• Authors: Todd Everson, Emory University; Carmen Marsit, Emory University; T.Micheal O'Shea, University of North Carolina; Amber Burt, Emory University; Karen Hermetz, Emory University; Brian S. Carter, Children's Mercy Hospital; Jennifer Helderman, Wake Forest School of Medicine; Julie A. Hofheimer, University of North Carolina; Elisabeth C. McGowan, Brown Alpert Medical School; Charles R. Neal, University of Hawaii; Steven L. Pastyrnak, Spectrum Health-Helen Devos Hospital; Lynne M. Smith, Harbor-UCLA Medical Center; Antoine Soliman, Miller Children's & Women's Hospital; Sheri A. DellaGrotta, Women & Infant's Hospital; Lynne M. Dansereau, Women & Infant's Hospital; James F. Padbury, Brown Alpert Medical School; Barry M. Lester, Brown Alpert Medical School
• Language: English
• Date: 2019-04-19
• Publisher: Nature Research (part of Springer Nature): Fully open access journals
• Publication Version: Final Published Version
• Copyright Statement: © 2019, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-019-42654-4
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 9
• Issue: 1
• Start Page: 6322
• End Page: 6322
• Grant/Funding Information: This work was supported by NIH Grants NICHD R01HD072267 (Lester and O’Shea); R01HD084515; and UH3OD023347 (Lester and Marsit).
• Keywords: DNA METHYLATION; Science & Technology - Other Topics; NEURODEVELOPMENTAL OUTCOMES; Science & Technology; Multidisciplinary Sciences; BRAIN-INJURY; MACROD2 GENE; CHILDREN; BEHAVIORAL OUTCOMES; RISK; GLUTAMATE RECEPTORS; AGE; LOW-BIRTH-WEIGHT
• Research Categories: Health Sciences, Public Health; Health Sciences, Medicine and Surgery

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.