The Peripheral Epigenome Predicts White Matter Volume Contingent on Developmental Stage: An ECHO Study

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.