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Novel Regions of Variable DNA Methylation in Human Placenta associated with Newborn Neurobehavioral Traits

ABSTRACT: Genome-wide profiling of placental DNA methylation in relation to neurobehavioral development. The Illumina 450k methylation array was used to profile 335 samples. These samples have been collected from the Rhode Island Child Health Study (RICHS).

ORGANISM(S): Homo sapiens

PROVIDER: GSE75248 | GEO | 2016/06/01

SECONDARY ACCESSION(S): PRJNA302897

REPOSITORIES: GEO

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Novel Regions of Variable DNA Methylation in Human Placenta associated with Newborn Neurobehavioral Traits

Project description:Genome-wide profiling of placental DNA methylation in relation to neurobehavioral development. The Illumina 450k methylation array was used to profile 335 samples. These samples have been collected from the Rhode Island Child Health Study (RICHS). Illumina analysis performed on 335 human placentas

2016-06-01 | E-GEOD-75248 | biostudies-arrayexpress

Epigenome-wide analyis of neurobehavioral variation in preterm infants

Project description: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 epigenomic measures from buccal cells were 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 DNA methylation (DNAm) levels at individual loci, measured via the Illumina EPIC microarray, differed between infants based on their NICU Network Neurobehavioral Scale (NNNS) profile classifications, ranging from most optimal to atypical. 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 in buccal cells may be informative for infant neurobehavior.

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DNA methylation and hydroxymethylation assessment through Illumina EPIC array analysis of paired bisulfite and oxidative-bisulfite conversion

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Regions of variable DNA methylation in human placenta associated with newborn neurobehavior.

Project description:The placenta regulates the in utero environment and functionally impacts fetal development. Candidate gene studies identified variation in placental DNA methylation is associated with newborn neurologic and behavioral outcomes including movement quality, lethargic behavior, attention, and arousal. We sought to identify novel regions of variable DNA methylation associated with newborn attention, lethargy, quality of movement, and arousal by performing an epigenome-wide association study in 335 infants from a US birth cohort. Methylation status was quantified using the Illumina HumanMethylation450 BeadChip array and associations to newborn outcomes assessed by the NICU Network Neurobehavioral Scales (NNNS) were identified while incorporating established bioinformatics algorithms to control for confounding by cell type composition. Methylation of CpGs within FHIT (cg15970800) and ANKRD11 (cg16710656) demonstrated genome-wide significance (P < 1.8 × 10(-7)) in specific associations with infant attention. CpGs whose differential methylation was associated with all 4 neurobehavioral outcomes were common to 50 genes involved in biological processes relating to cellular adhesion and nervous system development. Comprehensive methylation profiling identified relationships between methylation of FHIT and ANKRD11, which have been previously linked to neurodevelopment and behavioral outcomes in genetic association studies. Subtle changes in DNA methylation of these genes within the placenta may impact normal variation of a newborn's ability to alter and track visual and auditory stimuli. Gene ontology analysis suggested that those genes with variable methylation related to these outcomes are over-represented in biological pathways involved in brain development and placental physiology, supportive of our hypothesis for a key role of the placenta in neurobehavioral outcomes.

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Rhode Island Child Health Study

Project description:Rhode Island Child Health Study

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Rhode Island Child Health Study

Project description:Rhode Island Child Health Study

| PRJNA454114 | ENA

Epigenome analysis of newborn placenta and cord blood samples

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