Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders
Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders
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DOI：
10.1038/s41467-020-17051-5
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发表时间：
2020-07-03
影响因子：
16.6
通讯作者：
Raznahan, Armin
中科院分区：
文献类型：
--
作者：
Seidlitz, Jakob;Nadig, Ajay;Raznahan, Armin
神经发育障碍具有遗传性成分，并且与脑解剖结构中的区域特异性改变相关。然而，目前尚不清楚神经发育障碍的遗传风险如何转化为空间模式的大脑脆弱性。在这里，我们整合了由基因组拷贝数变异（CNVs）引起的神经发育障碍患者的皮质神经影像学数据和健康受试者的基因表达数据。对于六个调查的疾病，我们表明，空间模式的皮质解剖结构的变化在青年与皮质空间表达的CNV基因在神经典型的成年人。通过将规范的大块组织皮质表达数据转化为细胞类型表达图，我们将每种分析疾病的解剖学变化图与特定的细胞类别以及它们表达的CNV区域基因联系起来。我们的研究结果揭示了神经遗传性疾病中将遗传风险映射到区域大脑变化的组织原则。我们的研究结果将使候选分子机制筛选现成的神经影像学数据。神经发育障碍相关的风险基因如何转化为空间模式的大脑脆弱性尚不清楚。在这里，作者表明，神经解剖学变化的疾病特异性模式与健康受试者的疾病风险基因的大脑表达图谱一致。
Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data. How neurodevelopmental disorder-associated risk genes are translated into spatially patterned brain vulnerabilities is unclear. Here, the authors show that disorder-specific patterns of neuroanatomical changes are aligned to brain expression maps of disease risk genes in healthy subjects.