Epigenetic signatures linking environmental exposure, cortical structure and psychiatric traits
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Environmental exposures influence the risk of psychiatric disorders, yet the biological mechanisms by which such experiences become embedded in brain structure remain poorly understood. The human cerebral cortex is crucial for cognition and emotional regulation, and variation in cortical thickness (CT) and surface area (SA) is linked to various behavioural and psychiatric traits. Here, we present a large-scale epigenome-wide association study that combines peripheral blood DNA methylation (DNAm) with MRI-derived cortical measures in over 7,400 individuals across 20 cohorts within the ENIGMA consortium. We identify mostly non-overlapping DNAm signatures associated with CT and SA, consistent with their distinct developmental and regulatory architectures. CT-associated CpGs are replicated across independent cohorts and are enriched for environmentally responsive regulatory elements and pathways associated with stress, metabolism, and immune signalling. In contrast, SA-associated CpGs cluster within chromatin-regulatory regions involved in early cortical development. Phenome-wide and Mendelian randomisation analyses reveal pleiotropic associations between DNAm, cortical structure, and psychiatric and cognitive traits. These findings suggest that peripheral DNAm captures environmentally sensitive biological processes that link exposure, cortical organisation, and behavioural vulnerability.
