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

Abstract

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.