Schizophrenia is a severe neuropsychiatric disorder with a longstanding history of neurobiological investigation. Although the underlying causal mechanisms remain unknown, early neurodevelopmental events have been implicated in pathogenesis, initially by epidemiological and circumstantial data but more recently by brain-specific molecular and genetic findings. Notably, genomic research has recently uncovered discrete risk variants and risk loci associated with schizophrenia, with the potential to elucidate disease mechanisms. This Review revisits the neurodevelopmental model of schizophrenia from a current genetics perspective, delineating the complex genetic basis of the disorder and highlighting gene expression and epigenetic analyses of post-mortem cortical tissue that suggest that early brain development mediates genetic risk associated with schizophrenia. Future functional genomics investigations will accordingly need to characterize schizophrenia risk loci in relevant neurodevelopmental models.

中文翻译：

---

精神分裂症神经发育起源的遗传见解

精神分裂症是一种严重的神经精神疾病，具有悠久的神经生物学研究历史。尽管潜在的原因机制仍然未知，但早期的神经发育事件已牵涉到发病机理中，最初是通过流行病学和环境数据，但最近是通过脑特异性分子和遗传学发现。值得注意的是，基因组研究最近发现了与精神分裂症相关的离散风险变异和风险位点，具有阐明疾病机制的潜力。这篇评论从当前的遗传学角度重新审视了精神分裂症的神经发育模型，描绘了该疾病的复杂遗传基础，并突出了死后皮质组织的基因表达和表观遗传学分析，这些结果表明早期大脑发育会介导与精神分裂症相关的遗传风险。因此，未来的功能基因组学研究将需要在相关的神经发育模型中表征精神分裂症的风险基因座。