DNA methylation and brain structure and function across the life course: A systematic review

Area of Science:

• Neuroscience and Genetics
• Investigates the interplay between epigenetics and neuroimaging

Background:

• Magnetic Resonance Imaging (MRI) advances brain structure and function understanding.
• Genome influences variations in human brain structure and function.
• DNA methylation (DNAm) is a key epigenetic mechanism.

Purpose of the Study:

• To systematically review and synthesize findings from studies associating DNA methylation (DNAm) with human brain structure and function measured by MRI.
• To identify patterns, consistencies, and limitations in the existing literature linking DNAm and MRI data across various neurological and psychiatric conditions.

Main Methods:

• Systematic literature search identifying 60 studies reporting associations between DNA methylation and human brain structure/function.
• Categorization of studies based on DNAm measurement (candidate loci vs. epigenome-wide) and MRI features (structural, diffusion, functional imaging).
• Analysis of reported DNAm-MRI associations across diverse conditions including neurodevelopmental disorders, major depression, schizophrenia, and neurodegeneration.

Main Results:

• Sixty studies reported associations between DNA methylation (DNAm) and MRI-derived brain features.
• Reported associations spanned neurodevelopment, psychiatric disorders (depression, schizophrenia, PTSD), substance use, ageing, stroke, and socio-emotional processing.
• The consistency between MRI features and differential DNAm was found to be modest.

Conclusions:

• Knowledge of MRI features associated with differential DNAm may enhance understanding of DNAm's role in brain health and disease.
• Substantial clinical and methodological heterogeneity exists in the literature.
• Caution is advised due to the lack of established conventions for linking DNAm and MRI data and identified sources of bias.