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

Yoonjung Yoonie Joo, Bo-Gyeom Kim, Gakyung Kim, Eunji Lee, Jungwoo Seo and Jiook Cha ()
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Yoonjung Yoonie Joo: Seoul National University
Bo-Gyeom Kim: Seoul National University
Gakyung Kim: Seoul National University
Eunji Lee: Seoul National University
Jungwoo Seo: Seoul National University
Jiook Cha: Seoul National University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63312-6

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