System Genetics Working Group, Department of Genetics, Stellenbosch University, Stellenbosch, South Africa; Department of Genetics, Stellenbosch University, Stellenbosch, South Africa.
System Genetics Working Group, Department of Genetics, Stellenbosch University, Stellenbosch, South Africa; Department of Genetics, Stellenbosch University, Stellenbosch, South Africa.
Mol Cell Neurosci. 2018 Apr;88:300-307. doi: 10.1016/j.mcn.2018.02.010. Epub 2018 Mar 2.
Considerable evidence suggests that autism spectrum disorders (ASD), schizophrenia (SCZ), bipolar disorder (BD) and obsessive-compulsive disorder (OCD) share a common molecular aetiology, despite their unique clinical diagnostic criteria. The aim of this study was therefore to determine and characterise the common and unique molecular architecture of ASD, SCZ, BD and OCD. Gene lists were obtained from previously published studies for ASD, BD, SCZ and for OCD. Genes identified to be common to all disorders, or unique to one specific disorder, were included for enrichment analyses using the web-server tool Enrichr. Ten genes were identified to be commonly associated with the aetiology of ASD, SCZ, BD and OCD. Enrichment analyses determined that these genes are predominantly involved in the dopaminergic and serotonergic pathways, the voltage-gated calcium ion channel gene network, folate metabolism, regulation of the hippo signaling pathway, and the regulation of gene silencing and expression. In addition to well-characterised and previously described pathways, regulation of the hippo signaling pathway was commonly associated with ASD, SCZ, BD and OCD, implicating neural development and neuronal maintenance as key in neuropsychiatric disorders. In contrast, a large number of previously associated genes were shown to be disorder-specific. And unique disorder-specific pathways and biological processes were presented for ASD, BD, SCZ and OCD aetiology. Considering the current global incidence and prevalence rates of mental health disorders, focus should be placed on cross-disorder commonalities in order to realise actionable and translatable results to combat mental health disorders.
大量证据表明，自闭症谱系障碍（ASD）、精神分裂症（SCZ）、双相情感障碍（BD）和强迫症（OCD）尽管具有独特的临床诊断标准，但具有共同的分子发病机制。因此，本研究旨在确定和描述 ASD、SCZ、BD 和 OCD 的共同和独特的分子结构。从先前发表的 ASD、BD、SCZ 和 OCD 研究中获得基因列表。使用 Enrichr 网络服务器工具对所有疾病共同相关或特定于一种特定疾病的基因进行富集分析。确定了 10 个基因与 ASD、SCZ、BD 和 OCD 的发病机制共同相关。富集分析确定这些基因主要参与多巴胺能和 5-羟色胺能途径、电压门控钙通道基因网络、叶酸代谢、 hippo 信号通路的调节以及基因沉默和表达的调节。除了众所周知的和以前描述的途径外， hippo 信号通路的调节与 ASD、SCZ、BD 和 OCD 共同相关，这表明神经发育和神经元维持是神经精神疾病的关键。相比之下，大量先前相关的基因被证明是疾病特异性的。并且为 ASD、BD、SCZ 和 OCD 的发病机制呈现了独特的疾病特异性途径和生物学过程。考虑到目前全球精神健康障碍的发病率和流行率，应关注跨障碍的共性，以实现针对精神健康障碍的可操作和可转化的结果。
