Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia-related genes
Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia-related genes
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DOI：
10.1073/pnas.1820754116
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发表时间：
2019-05-07
影响因子：
11.1
通讯作者：
Bullmore, Edward T.
中科院分区：
文献类型：
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作者：
Morgan, Sarah E.;Seidlitz, Jakob;Bullmore, Edward T.
精神分裂症一直被认为是一种大脑连通性障碍，但目前尚不清楚这种网络表型如何与潜在的遗传学相关。在之前的三个精神病病例对照研究中，我们使用MRI数据的形态相似性分析作为区域间皮质连通性的标记：总共有n = 185例病例和n = 227例对照。在所有三项研究中，精神病与整体形态相似性降低有关。在区域形态测量相似性方面也存在可复制的病例对照差异模式，额叶和颞叶皮质区的相似性显著降低，而顶叶皮质区的相似性增加。利用先前的全脑基因表达数据，我们发现形态学相似性的病例对照差异的皮质图谱在空间上与丰富神经生物学相关本体术语和通路的加权基因组合的皮质表达相关。此外，在先前的三项精神分裂症死后研究中，通常在形态相似性降低的皮质区域过度表达的基因显着上调。我们提出，这种神经成像和转录数据的结合分析提供了对先前涉及的基因和蛋白质以及蛋白质相互作用网络拓扑附近的一些未报道的基因如何驱动结构脑网络变化介导精神分裂症遗传风险的见解。
Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics. We used morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case-control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies. There was also a replicable pattern of case-control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex. Using prior brain-wide gene expression data, we found that the cortical map of case-control differences in morphometric similarity was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms and pathways. In addition, genes that were normally overexpressed in cortical areas with reduced morphometric similarity were significantly up-regulated in three prior post mortem studies of schizophrenia. We propose that this combined analysis of neuroimaging and transcriptional data provides insight into how previously implicated genes and proteins as well as a number of unreported genes in their topological vicinity on the protein interaction network may drive structural brain network changes mediating the genetic risk of schizophrenia.