Commonality in dysregulated expression of gene sets in cortical brains of individuals with autism, schizophrenia, and bipolar disorder
Commonality in dysregulated expression of gene sets in cortical brains of individuals with autism, schizophrenia, and bipolar disorder
复制标题
自闭症、精神分裂症和双相情感障碍患者大脑皮层基因组表达失调的共性
DOI：
10.1038/s41398-019-0488-4
复制
发表时间：
2019-05-24
影响因子：
6.8
通讯作者：
Sham, Pak Chung
中科院分区：
文献类型：
--
作者：
Guan, Jinting;Cai, James J.;Sham, Pak Chung
患有不同神经精神障碍的人，如自闭症(AUT)、精神分裂症(SCZ)和双相情感障碍(BPD)，可能有相似的临床表现，这表明这些疾病背后有共同的遗传影响和共同的生物机制。使用从受AUT、SCZ和BPD影响的死后捐赠者收集的脑转录组数据，现在可以识别共享的失调基因集，即与非精神病对照组相比，神经精神病患者大脑中异常表达的基因。在这里，我们应用一种新的异常基因表达分析方法，结合共识共表达网络分析，在AUT、SCZ和BPD患者的大脑皮层中识别共同表达异常的基因集。我们鉴定了AUT、SCZ和BPD共有的8个基因表达异常，AUT和SCZ共有23个，AUT和BPD共有4个，SCZ和BPD共有2个。已鉴定的基因具有丰富的功能，涉及氨基酸转运、突触、神经递质释放、氧化应激、一氧化氮合酶生物合成、免疫反应、蛋白质折叠、溶血磷脂酸介导的信号转导和糖酵解。我们的方法已经被证明在发现和揭示不同神经精神障碍共享的表达异常的多基因集方面是有效的。我们的发现为AUT、SCZ和BPD的发病和进展的共同分子机制提供了新的见解，有助于研究这些神经精神疾病之间的病因重叠。
Individuals affected with different neuropsychiatric disorders such as autism (AUT), schizophrenia (SCZ) and bipolar disorder (BPD), may share similar clinical manifestations, suggesting shared genetic influences and common biological mechanisms underlying these disorders. Using brain transcriptome data gathered from postmortem donors affected with AUT, SCZ and BPD, it is now possible to identify shared dysregulated gene sets, i.e., those abnormally expressed in brains of neuropsychiatric patients, compared to non-psychiatric controls. Here, we apply a novel aberrant gene expression analysis method, coupled with consensus co-expression network analysis, to identify gene sets with shared dysregulated expression in cortical brains of individuals affected with AUT, SCZ and BPD. We identify eight gene sets with dysregulated expression shared by AUT, SCZ and BPD, 23 by AUT and SCZ, four by AUT and BPD, and two by SCZ and BPD. The identified genes are enriched with functions relevant to amino acid transport, synapse, neurotransmitter release, oxidative stress, nitric oxide synthase biosynthesis, immune response, protein folding, lysophosphatidic acid-mediated signaling and glycolysis. Our method has been proven to be effective in discovering and revealing multigene sets with dysregulated expression shared by different neuropsychiatric disorders. Our findings provide new insights into the common molecular mechanisms underlying the pathogenesis and progression of AUT, SCZ and BPD, contributing to the study of etiological overlap between these neuropsychiatric disorders.