Polygenic architecture of brain structure and function, behaviors, and psychopathologies in children

Childhood brain development involves dynamic remodeling shaped by genetic influences contributing to long-term neurodevelopmental variation. Here we report integrative analyses of over 8600 children, using 7 brain imaging-derived phenotype (IDP) modalities, polygenic scores (PGS) of 33 complex traits, and 266 cognitive and psychological phenotypes. Most brain IDPs show low-to-moderate SNP-based heritability, lower than typically observed in adults. Sparse generalized canonical correlation analysis reveals positive associations between cognitive-related PGS and structural MRI features (e.g., total grey matter and ventral diencephalon volumes) and N-back task-related activation, while PGS for ADHD, depression, and neuroticism showed negative associations. Cognitive PGS also correlates positively with diffusion MRI metrics (streamline counts, fractional anisotropy in subcortical-frontal tracts and inferior parietal–subcortical tracts), whereas health-risk PGS (e.g., BMI, ADHD) correlates negatively. This study delineates key gene–brain–behavior associations in preadolescence, providing a multivariate dissection of the polygenic architecture underlying neurodevelopment. This study reveals how genetic profiles shape brain structure, function, and behavior in over 8,600 children, linking polygenic scores to key brain imaging features and cognitive traits during early neurodevelopment.