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

Author

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  • Yoonjung Yoonie Joo

    (Seoul National University
    Sungkyunkwan University
    Samsung Medical Center)

  • 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
    Seoul National University
    Seoul National University
    Seoul National University)

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.

Suggested Citation

  • Yoonjung Yoonie Joo & Bo-Gyeom Kim & Gakyung Kim & Eunji Lee & Jungwoo Seo & Jiook Cha, 2025. "Polygenic architecture of brain structure and function, behaviors, and psychopathologies in children," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63312-6
    DOI: 10.1038/s41467-025-63312-6
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