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Sci Rep. 2019 Apr 19;9(1):6322. doi: 10.1038/s41598-019-42654-4.

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

Author information

1
Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, United States. Todd.M.Everson@Emory.edu.
2
Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, United States.
3
Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, United States.
4
Department of Pediatrics-Neonatology, Children's Mercy Hospital, Kansas City, MO, United States.
5
Department of Pediatrics, Wake Forest School of Medicine, Winston Salem, NC, United States.
6
Department of Pediatrics, Brown Alpert Medical School and Women and Infants Hospital, Providence, RI, United States.
7
Department of Pediatrics, University of Hawaii John A. Burns School of Medicine, Honolulu, HI, United States.
8
Department of Pediatrics, Spectrum Health-Helen Devos Hospital, Grand Rapids, MI, United States.
9
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, United States.
10
Department of Pediatrics, Miller Children's and Women's Hospital Long Beach, Long Beach, CA, United States.
11
Brown Center for the Study of Children at Risk, Brown Alpert Medical School and Women and Infants Hospital, Providence, RI, United States.
12
Department of Psychiatry and Human Behavior, Brown Alpert Medical School, Providence, RI, United States.

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.

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