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The Peripheral Epigenome Predicts White Matter Volume Contingent on Developmental Stage: An ECHO Study
Taena Hanson1, Sophie Spencer1, Samantha A Harker1
1School of Life Sciences and Psychology, Arizona State University, Tempe, AZ, 85287, USA.
Insights
Peripheral DNA methylation (DNAm) in saliva tracks white matter volume (WMV) in children, offering potential for early disorder detection. These epigenetic markers are crucial for understanding neurodevelopmental trajectories.
Area of Science:
- Neuroscience
- Epigenetics
- Developmental Biology
Background:
- White matter (WM) development is vital for neural connectivity, and its disruptions are linked to neurodevelopmental disorders.
- Epigenetic mechanisms, specifically DNA methylation (DNAm), are increasingly recognized for their role in regulating WM structure.
- Limited research exists on DNAm and WM development in pediatric populations.
Purpose of the Study:
- To investigate the association between peripheral DNAm of WM-related genes and WM volume (WMV) in children.
- To explore age-dependent relationships between DNAm and WMV.
- To assess the correlation between salivary DNAm and brain tissue DNAm.
Main Methods:
- Utilized data from the Environmental Influences on Child Health Outcomes (ECHO) study.
- Obtained salivary DNAm profiles from 205 children (2 months–15.5 years) using the Infinium MethylationEPIC array.
- Quantified WMV using T1-weighted MRI and performed targeted-epigenome analysis.
Main Results:
- Identified 1867 CpG sites across 352 genes significantly predicting WMV (FDR q < 0.05).
- Found 11,611 CpG sites with age-dependent associations, most pronounced in early childhood.
- Demonstrated a strong correlation between salivary DNAm and brain tissue DNAm (r = 0.915).
Conclusions:
- Peripheral DNAm markers in saliva can serve as biomarkers for neurodevelopmental trajectories.
- Saliva-based DNAm is a valuable tool for pediatric neuroimaging research.
- Developmental timing is critical for understanding DNAm-WMV associations, with implications for early detection of WM disorders.
Abstract:
White matter (WM) development is crucial for efficient neural connectivity, and disruptions in its maturation are associated with neurocognitive and psychiatric disorders. Emerging evidence suggests that epigenetic mechanisms, particularly DNA methylation (DNAm), regulate WM structure, yet little is known about these relationships in pediatric populations. Using data from the Environmental Influences on Child Health Outcomes (ECHO) study, we investigated the association between peripheral DNAm of WM-related genes and WM volume (WMV) across development. Salivary DNAm profiles were obtained from 205 children (2 months-15.5 years) using the Infinium MethylationEPIC array, and T1-weighted MRI was used to quantify WMV. A targeted-epigenome analysis identified 1867 CpG sites across 352 genes significantly predicting WMV (FDR q < 0.05). Notably, 11,611 CpG sites exhibited age-dependent associations, with effects strongest in early childhood. Further, DNAm in saliva significantly correlated with DNAm in brain tissue (r = 0.915). These findings suggest that peripheral epigenetic markers may serve as biomarkers of neurodevelopmental trajectories, with potential applications in early detection of WM-related disorders. Our study highlights the importance of developmental timing in DNAm-WMV associations and underscores the utility of saliva-based DNAm in pediatric neuroimaging research.
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