Multivariate patterns between brain network properties, polygenic scores, phenotypes, and environment in preadolescents

Brain development in childhood is shaped by complex interactions between genetic predispositions, environmental influences, and neural connectivity, yet how these factors jointly contribute to cognitive and mental health outcomes remains unclear. Structural brain networks, quantified through graph-theoretic measures, have been linked to cognition and psychiatric risk, but the extent to which genetic architecture and environmental exposures shape these networks, and whether brain networks mediate these influences, is not well understood. Here we show that genetic predispositions related to cognitive ability and socioeconomic status (SES) exhibit the strongest covariation with structural brain network topology in children. Using sparse canonical correlation analysis (SCCA) on ABCD Study data (N = 10,343), we identified robust associations between brain network properties, polygenic scores for cognition, SES indicators, and cognitive-psychopathological phenotypes. Mediation analysis further demonstrated that structural brain networks partially mediate the influence of genetic and environmental factors on cognitive performance and mental health outcomes, suggesting that neurodevelopmental trajectories may be shaped by both genetic liability and modifiable environmental conditions. These findings provide empirical support for a multivariate, systems-level perspective on brain development and cognitive-psychopathological variation in youth. By elucidating shared neural substrates underlying genetic and environmental influences, this work advances our understanding of brain network development and highlights potential pathways for individualized interventions and predictive modeling in developmental psychiatry and neuroscience.