Departments of Radiology and Psychiatry, Division of Neuroradiology, Brain Behavior Laboratory, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104,
Departments of Psychiatry and Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia 23298.
J Neurosci. 2019 Apr 17;39(16):3028-3040. doi: 10.1523/JNEUROSCI.2248-18.2019. Epub 2019 Mar 4.
The genetics of cortical arealization in youth is not well understood. In this study, we use a genetically informative sample of 677 typically developing children and adolescents (mean age 12.72 years), high-resolution MRI, and quantitative genetic methodology to address several fundamental questions on the genetics of cerebral surface area. We estimate that >85% of the phenotypic variance in total brain surface area in youth is attributable to additive genetic factors. We also observed pronounced regional variability in the genetic influences on surface area, with the most heritable areas seen in primary visual and visual association cortex. A shared global genetic factor strongly influenced large areas of the frontal and temporal cortex, mirroring regions that are the most evolutionarily novel in humans relative to other primates. In contrast to studies on older populations, we observed statistically significant genetic correlations between measures of surface area and cortical thickness ( = 0.63), suggestive of overlapping genetic influences between these endophenotypes early in life. Finally, we identified strong and highly asymmetric genetically mediated associations between Full-Scale Intelligence Quotient and left perisylvian surface area, particularly receptive language centers. Our findings suggest that spatially complex and temporally dynamic genetic factors are influencing cerebral surface area in our species. Over evolution, the human cortex has undergone massive expansion. In humans, patterns of neurodevelopmental expansion mirror evolutionary changes. However, there is a sparsity of information on how genetics impacts surface area maturation. Here, we present a systematic analysis of the genetics of cerebral surface area in youth. We confirm prior research that implicates genetics as the dominant force influencing individual differences in global surface area. We also find evidence that evolutionarily novel brain regions share common genetics, that overlapping genetic factors influence both area and thickness in youth, and the presence of strong genetically mediated associations between intelligence and surface area in language centers. These findings further elucidate the complex role that genetics plays in brain development and function.
年轻人大脑皮层区域化的遗传学尚不清楚。在这项研究中，我们使用了一个具有遗传信息的 677 名典型发育的儿童和青少年（平均年龄 12.72 岁）样本，高分辨率 MRI 和定量遗传方法，来解决关于大脑表面积遗传学的几个基本问题。我们估计，年轻人总脑表面积的表型方差超过 85%归因于加性遗传因素。我们还观察到，大脑表面积的遗传影响存在明显的区域变异性，最具遗传性的区域见于初级视觉和视觉联合皮层。一个共同的全局遗传因素强烈影响了额和颞叶皮层的大部分区域，反映了与其他灵长类动物相比，人类大脑中最具进化新颖性的区域。与对老年人的研究不同，我们观察到大脑表面积和皮层厚度之间的遗传相关性具有统计学意义（ = 0.63），提示这些表型在生命早期存在重叠的遗传影响。最后，我们发现全脑智商与左侧侧脑室周围表面积之间存在强烈而高度不对称的遗传介导关联，特别是在接受性语言中心。我们的研究结果表明，空间复杂和时间动态的遗传因素正在影响我们物种的大脑表面积。在进化过程中，人类大脑经历了大规模扩张。在人类中，神经发育扩张模式反映了进化变化。然而，关于遗传如何影响表面积成熟的信息很少。在这里，我们对年轻人大脑表面积的遗传学进行了系统分析。我们证实了先前的研究，即遗传是影响全球表面积个体差异的主要因素。我们还发现，进化新颖的大脑区域具有共同的遗传，重叠的遗传因素在年轻人中同时影响面积和厚度，以及智力和语言中心表面积之间存在强烈的遗传介导关联。这些发现进一步阐明了遗传在大脑发育和功能中的复杂作用。
