Title: Cord blood DNA methylation modifications in infants are associated with white matter microstructure in the context of prenatal maternal depression and anxiety
Legend: Gene pathways analysis of differentially methylation position (DMP) in CB that were associated infant WM microstructure-related changes (νIC) showing a Sex x Symptom interaction. (Left) Bar Graph of the top 20 gene ontological (GO) biological processes associated with the differentially methylated genes, ordered by statistical significance. X-axis indicates the number of DMP-associated genes contributing to each GO term. The shade of the bars shows the p value based on the legend, as determined by a Fischer test. Neg. = Negative; Pos. = Positive. (Right) An enrichment map plot depicts the connectivity of associated terms, with hubs of similar processes clustering further apart. Node (spheres) size represent the relative number of DMP-associated genes contributing to each term, while the color represents the FDR p-value, shown in the legend, as determined by a Fischer test. The size of the edges (gray lines) depicts the strength of relatedness between terms.
Citation: Dean, D.C., Madrid, A., Planalp, E.M. et al. Cord blood DNA methylation modifications in infants are associated with white matter microstructure in the context of prenatal maternal depression and anxiety. Science Reports, 11, 12181 (2021).
Abstract: Maternal and environmental factors influence brain networks and architecture via both physiological pathways and epigenetic modifications. In particular, prenatal maternal depression and anxiety symptoms appear to impact infant white matter (WM) microstructure, leading us to investigate whether epigenetic modifications (i.e., DNA methylation) contribute to these WM differences. To determine if infants of women with depression and anxiety symptoms exhibit epigenetic modifications linked to neurodevelopmental changes, 52 umbilical cord bloods (CBs) were profiled. We observed 219 differentially methylated genomic positions (DMPs; FDR p < 0.05) in CB that were associated with magnetic resonance imaging measures of WM microstructure at 1 month of age and in regions previously described to be related to maternal depression and anxiety symptoms. Genomic characterization of these associated DMPs revealed 143 unique genes with significant relationships to processes involved in neurodevelopment, GTPase activity, or the canonical Wnt signaling pathway. Separate regression models for female (n = 24) and male (n = 28) infants found 142 associated DMPs in females and 116 associated DMPs in males (nominal p value < 0.001, R > 0.5), which were annotated to 98 and 81 genes, respectively. Together, these findings suggest that umbilical CB DNA methylation levels at birth are associated with 1-month WM microstructure.
About the Lab: Doug’s research focuses on the development and application of novel quantitative magnetic resonance imaging (MRI) methods to measure and evaluate the brain structure throughout early neurodevelopment and aging. He is particularly experienced in pediatric imaging, scanning more than 800 infants and young children (3 months to 12 years) during his graduate work. His current research is focused on examining how the white matter microstructure of the brain develops across the early development and how these microstructural processes are related to changes in cognition and behavior. Visit the Developing Brain Imaging Lab.