Biological Determinants of Brain Variation in Autism

描述（由申请人提供）：这项拟议研究的目标是产生大脑发育的遗传结构。我们打算分两个坚实的步骤实现这一目标。我们首先利用现有的大脑磁共振成像测量（传统的MRI体积测量，大脑连通性，静息状态活动），对235名个体，125名自闭症患者和110名典型发展受试者，建立了一个对典型大脑具有至少50%估计遗传率的感兴趣的大脑区域的数据结构，首先按大小排序，然后按结构-功能变异性的组成部分排序。在我们的下一步，我们询问全外显子组和全基因组序列和网络分析的分子途径通过最先进的分子遗传学方法参考这个数据结构。我们期望对自闭症患者脑成像表型的变异性和极端的详细分析将导致发现新的遗传关联，揭示新的生物学途径，并推进我们对自闭症神经病理学及其严重损害的临床表现的理解。因此，我们的研究结果将改变自闭症研究中的成像遗传学。

DESCRIPTION (provided by applicant): The goal of this proposed research is to generate a genetic architecture of brain development. We aim to achieve this goal in two solid steps. We first utilize our existing brain MR imaging measurements (traditional MRI volumetry, brain connectivity, resting state activity) of 235 individuals, 125 with autism and 110 typically developing subjects, to build a data structure of brain regions of interest that have at least 50% estimated heritability for typical brains, sorted first by size and then by components of structura-functional variability. In our next step, we interrogate whole-exome and whole-genome sequences and network analysis of molecular pathways by state-of-the-art molecular genetics methods in reference to this data structure. We expect that this detailed analysis of variability and extremes in brain imaging phenotypes in autism will result in the discovery of new genetic associations that reveal new biological pathways and advance our understanding of autism neuropathology and its severely impairing clinical manifestations. Our results will thus change imaging genetics in autism research.