Departments of Psychiatry and Radiology, Division of Neuroradiology, Brain Behavior Laboratory, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Department of Psychiatry, CHOP-Penn Brain-Gene-Development Laboratory, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Commun Biol. 2024 Oct 10;7(1):1301. doi: 10.1038/s42003-024-06956-2.
Prior studies have shown strong genetic effects on cortical thickness (CT), structural covariance, and neurodevelopmental trajectories in childhood and adolescence. However, the importance of genetic factors on the induction of spatiotemporal variation during neurodevelopment remains poorly understood. Here, we explore the genetics of maturational coupling by examining 308 MRI-derived regional CT measures in a longitudinal sample of 677 twins and family members. We find dynamic inter-regional genetic covariation in youth, with the emergence of regional subnetworks in late childhood and early adolescence. Three critical neurodevelopmental epochs in genetically-mediated maturational coupling were identified, with dramatic network strengthening near eleven years of age. These changes are associated with statistically-significant (empirical p-value <0.0001) increases in network strength as measured by average clustering coefficient and assortativity. We then identify genes from the Allen Human Brain Atlas with similar co-expression patterns to genetically-mediated structural covariation in children. This set was enriched for genes involved in potassium transport and dendrite formation. Genetically-mediated CT-CT covariance was also strongly correlated with expression patterns for genes located in cells of neuronal origin.
先前的研究表明，皮质厚度（CT）、结构协方差和儿童及青少年时期的神经发育轨迹受强烈的遗传因素影响。然而，遗传因素在神经发育过程中诱导时空变化的重要性仍知之甚少。在这里，我们通过检查 677 对双胞胎和家庭成员的纵向样本中的 308 个 MRI 衍生的区域 CT 测量值，探索成熟耦合的遗传学。我们发现青少年时期存在动态的区域间遗传共变，在儿童后期和青少年早期出现了区域子网络。在遗传介导的成熟耦合中确定了三个关键的神经发育时期，在 11 岁左右网络强度显著增强。这些变化与网络强度的显著增加相关，这是通过平均聚类系数和聚集度来衡量的。然后，我们从艾伦人类大脑图谱中识别出与儿童中遗传介导的结构协变具有相似共表达模式的基因。这一组富集了涉及钾转运和树突形成的基因。CT-CT 的遗传协变与位于神经元起源细胞中的基因的表达模式也有很强的相关性。
