Abstract
There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112) and European American (EA; N = 91) participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood). Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition—specifically, plasma levels of vitamin D and folate during pregnancy—on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC). Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome.
Highlights
Epigenetics refer to a host of molecular mechanisms that can influence phenotypes by regulating gene expression
We obtained the full list of uncorrected p-values and used this to evaluate how many of the differentially methylated sites we identified in CANDLE at FDR 5% are differentially methylated in the HapMap panel using these criteria: (1) uncorrected p-value 0.05 between YRI and CEU, and (2) consistency in either higher or lower methylation in African ancestry in both the CANDLE and HapMap groups
Since maternal age and blood cell counts have significant influence on DNA methylation [19, 37] and both show significant difference between AA and European American (EA) in CANDLE (Table 1), these were included as covariates
Summary
Epigenetics refer to a host of molecular mechanisms that can influence phenotypes by regulating gene expression. Much of the research on the epigenome has focused on DNA methylation, partly because methylation is far more amenable to high-throughput and semiquantitative genome-wide assessments using microarrays. The epigenome-wide surveys have characterized significant inter-individual variability that likely results from a combination of PLOS ONE | DOI:10.1371/journal.pone.0118466. Maternal Nutrition and DNA Methylation in Neonates. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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