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bioRxiv
BIORXIV
bioRxiv
Cold Spring Harbor Laboratory

10.1101/2024.05.22.595444
preprint
1
Article
Polygenic architecture of brain structure and function, behaviors, and psychopathologies in children
Joo Yoonjung Yoonie http://orcid.org/0000-0001-9506-8742

Lee Eunji http://orcid.org/0000-0002-2589-5395

Kim Bo-Gyeom http://orcid.org/0000-0003-2685-877X

Kim Gakyung http://orcid.org/0000-0002-3729-081X

Seo Jungwoo http://orcid.org/0009-0002-9008-1678

Cha Jiook http://orcid.org/0000-0002-5314-7992

23 5 2024
2024.05.22.595444http://biorxiv.org/lookup/doi/10.1101/2024.05.22.595444
nihpp-2024.05.22.595444.pdf
Abstract

The human brain undergoes structural and functional changes during childhood, a critical period in cognitive and behavioral development. Understanding the genetic architecture of the brain development in children can offer valuable insights into the development of the brain, cognition, and behaviors. Here, we integrated brain imaging-genetic-phenotype data from over 8,600 preadolescent children of diverse ethnic backgrounds using multivariate statistical techniques. We found a low-to-moderate level of SNP-based heritability in most IDPs, which is lower compared to the adult brain. Using sparse generalized canonical correlation analysis (SGCCA), we identified several covariation patterns among genome-wide polygenic scores (GPSs) of 29 traits, 7 different modalities of brain imaging-derived phenotypes (IDPs), and 266 cognitive and psychological phenotype data. In structural MRI, significant positive associations were observed between total grey matter volume, left ventral diencephalon volume, surface area of right accumbens and the GPSs of cognition-related traits. Conversely, negative associations were found with the GPSs of ADHD, depression and neuroticism. Additionally, we identified a significant positive association between educational attainment GPS and regional brain activation during the N-back task. The BMI GPS showed a positive association with fractional anisotropy (FA) of connectivity between the cerebellum cortex and amygdala in diffusion MRI, while the GPSs for educational attainment and cannabis use were negatively associated with the same IDPs. Our GPS-based prediction models revealed substantial genetic contributions to cognitive variability, while the genetic basis for many mental and behavioral phenotypes remained elusive. This study delivers a comprehensive map of the relationships between genetic profiles, neuroanatomical diversity, and the spectrum of cognitive and behavioral traits in preadolescence.
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pmc
