In the past decade, the identification of susceptibility genes for psychiatric disorders has become routine, but understanding the biology underlying these discoveries has proven extremely difficult. The large number of potential risk genes and the genetic overlap between disorders are major obstacles for studying the etiology of these conditions. Systems biology approaches relying on gene ontologies, gene coexpression, and protein-protein interactions are used to identify convergence of the genes in relation to biological processes, cell types, brain areas, and developmental stages. Across psychiatric disorders, there is a clear enrichment for genes expressed in the brain and especially in the cortex, but a higher resolution is vastly dependent on sample size and statistical power. There is indication that susceptibility genes tend to be expressed in the brain during periods preceding the typical onset of the disorders. Thus, the role of genes in prenatal brain development is more pronounced for childhood-onset disorders, such as autism spectrum disorder and attention-deficit/hyperactivity disorder, but is much less so for bipolar disorder and depression. One of the most consistent findings across multiple disorders and classes of genetic variants is the role of genes intolerant to mutations in psychiatric disorders, yet this association is more pronounced for disorders with a clear neurodevelopmental component. Notwithstanding, a detailed understanding of the neurobiology of psychiatric disorders is still lacking. It is possible that it will only be revealed by studying the risk genes at the level of the development and function of neuronal networks and circuits.

中文翻译：

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精神疾病从途径到发育阶段的遗传学的趋同和发散

在过去的十年中，鉴定精神疾病的易感基因已成为常规，但已证明了解这些发现背后的生物学非常困难。大量潜在风险基因和疾病之间的遗传重叠是研究这些疾病病因的主要障碍。系统生物学方法依赖于基因本体、基因共表达和蛋白质-蛋白质相互作用，用于识别与生物过程、细胞类型、大脑区域和发育阶段相关的基因的融合。在精神疾病中，大脑尤其是皮层中表达的基因明显富集，但更高的分辨率在很大程度上取决于样本量和统计能力。有迹象表明，易感基因倾向于在疾病典型发作之前的时期在大脑中表达。因此，基因在产前大脑发育中的作用在儿童期发病的疾病中更为明显，例如自闭症谱系障碍和注意力缺陷/多动障碍，但对双相情感障碍和抑郁症的作用要小得多。在多种疾病和遗传变异类别中，最一致的发现之一是不耐受基因突变的基因在精神疾病中的作用，但这种关联对于具有明确神经发育成分的疾病更为明显。尽管如此，仍然缺乏对精神疾病的神经生物学的详细了解。