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首页> 外文期刊>Journal of genetics >Meta-analysis of genomic variants and gene expression data in schizophrenia suggests the potential need for adjunctive therapeutic interventions for neuropsychiatric disorders
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Meta-analysis of genomic variants and gene expression data in schizophrenia suggests the potential need for adjunctive therapeutic interventions for neuropsychiatric disorders

机译：基因组变体和精神分裂症中基因表达数据的荟萃分析表明神经精神疾病的辅助治疗干预措施的潜在需求

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Schizophrenia (SZ) is a debilitating mental illness with a multigenic aetiology and significant heritability. Despite extensive genetic studies, the molecular aetiology has remained enigmatic. A recent systems biology study suggested a protein-protein interaction network for SZ with 504 novel interactions. The onset of psychiatric disorders is predominant during adolescence, often accompanied by subtle structural abnormalities in multiple regions of the brain. The availability of BrainSpan Atlas data allowed us to re-examine the genes present in the SZ interactome as a function of space and time. The availability of genomes of healthy centenarians and nonpsychiatric Exome Aggregation Consortium database allowed us to identify the variants of criticality. The expression of the SZ candidate genes responsible for cognition and disease onset was studied in different brain regions during particular developmental stages. A subset of novel interactors detected in the network was further validated using gene expression data of post-mortem brains of patients with psychiatric illness. We have narrowed down the list of drug targets proposed by the previous interactome study to 10 proteins. These proteins belonging to 81 biological pathways are targeted by 34 known Food and Drug Administration-approved drugs that have distinct potential for the treatment of neuropsychiatric disorders. We also report the possibility of targeting key genes belonging to celecoxib pharmacodynamics, G signalling and cGMP-PKG signalling pathways that are not known to be specific to SZ aetiology.
机译：精神分裂症（SZ）是一种令人衰弱的精神疾病，具有多脂疾病和显着的遗传性。尽管遗传研究广泛，但分子aetiology仍然存在神秘。最近的系统生物学研究表明，SZ的蛋白质 - 蛋白质相互作用网络，具有504个新的相互作用。精神疾病发病在青春期期间是主要的，通常伴随着大脑多个区域的细微结构异常。 BrainsPan Atlas数据的可用性使我们能够重新检查SZ互联体中存在的基因，作为空间和时间的函数。健康百岁老人和非精神科极端聚合联盟数据库的基因组的可用性使我们能够识别临界的变种。在特定的发展阶段，在不同脑区中研究了负责认知和疾病发作的SZ候选基因的表达。使用精神疾病患者的验尸大脑的基因表达数据进一步验证了网络中检测到网络中检测到的新型交互运动的子集。我们已经缩小了先前的互动研究提出的药物目标列表到10种蛋白质。这些属于81个生物途径的蛋白质由34种已知的食品和药物给药批准的药物靶向，该药物具有明显的治疗神经精神疾病的可能性。我们还报告了靶向属于Celecoxib药效学，G信令和CGMP-PKG信号传导途径的关键基因的可能性，该途径不知道特异于SZ Aetiology。

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