Joo Yoonjung Yoonie, Lee Eunji, Kim Bo-Gyeom, Kim Gakyung, Seo Jungwoo, Cha Jiook
Department of Psychology, Seoul National University.
Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea.
bioRxiv. 2024 May 23:2024.05.22.595444. doi: 10.1101/2024.05.22.595444.
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.
人类大脑在童年时期会经历结构和功能上的变化，这是认知和行为发展的关键时期。了解儿童大脑发育的遗传结构可以为大脑、认知和行为的发展提供有价值的见解。在这里，我们使用多变量统计技术整合了来自8600多名不同种族背景的青春期前儿童的脑成像-遗传-表型数据。我们发现，大多数影像诊断学特征基于单核苷酸多态性的遗传度处于低到中等水平，与成人大脑相比更低。使用稀疏广义典型相关分析（SGCCA），我们在29种性状的全基因组多基因评分（GPS）、7种不同模式的脑成像衍生表型（影像诊断学特征）和266项认知与心理表型数据之间识别出了几种共变模式。在结构磁共振成像中，观察到总灰质体积、左侧腹侧间脑体积、右侧伏隔核表面积与认知相关性状的GPS之间存在显著正相关。相反，发现与注意力缺陷多动障碍、抑郁症和神经质的GPS呈负相关。此外，我们发现教育程度GPS与N-back任务期间的区域脑激活之间存在显著正相关。身体质量指数GPS在扩散磁共振成像中显示与小脑皮质和杏仁核之间的连接分数各向异性（FA）呈正相关，而教育程度和大麻使用的GPS与相同的影像诊断学特征呈负相关。我们基于GPS的预测模型揭示了遗传因素对认知变异性的重大贡献，而许多心理和行为表型的遗传基础仍然难以捉摸。这项研究提供了一幅关于青春期前遗传特征、神经解剖学多样性以及认知和行为特征谱之间关系的综合图谱。
