Enrichment of rare genetic variants in astrocyte gene enriched co-expression modules altered in postmortem brain samples of schizophrenia
Enrichment of rare genetic variants in astrocyte gene enriched co-expression modules altered in postmortem brain samples of schizophrenia
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DOI：
10.1016/j.nbd.2018.10.013
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发表时间：
2019-01-01
影响因子：
6.1
通讯作者：
Xu, Bin
中科院分区：
文献类型：
--
作者：
Gonzalez-Penas, Javier;Costas, Javier;Xu, Bin
采用综合方法研究了一组特征明确的精神分裂症患者（SCZ）和匹配对照的死后脑组织扣带回区域的转录组谱，该方法分析了转录表达模式的改变和表达基因中的罕见遗传变异。我们证明了增加表达的星形胶质细胞相关基因使用时空共表达模块，以前已经建立了开发人脑，并显示这些结果是独立的药物剂量。进一步研究了神经发育背景下遗传变异和表达模式之间的关系，我们在一组特异于星形胶质细胞的标记基因中发现了罕见遗传变异的富集，并在SCZ患者中上调。我们的研究结果表明，星形胶质细胞功能障碍参与SCZ的病理生理。此外，我们的方法表明了一种新的策略，将可能导致SCZ患者病理生理学的遗传变异缩小到在受影响的大脑区域高度表达的基因子集。
The transcriptome profiles of the cingulate gyrus region from the postmortem brain tissues of a set of well characterized patients with schizophrenia (SCZ) and matched controls were investigated using an integrated approach that analyzed both the alterations in transcription expression pattern and rare genetic variants in expressed genes. We demonstrated increased expression of astrocyte-related genes using spatiotemporal co-expression modules that have previously been established for developing human brain, and showed these results are independent of medication dosage. The relationship between genetic variants and expression pattern in the context of neurodevelopment was further investigated, and we identified an enrichment of rare genetic variants in a set of signature genes that were specific to astrocytes and up-regulated in the patients with SCZ. Our result suggested the involvement of astrocyte malfunction in SCZ pathophysiology. In addition, our approach indicated a novel strategy of narrowing down genetic variants that might contribute to the pathophysiology in the patients with SCZ to a subset of genes that are highly expressed in an affected brain region.