Cell-specific genetic regulatory mechanisms mediating risk for neuropsychiatric disorders in the developing human brain

精神疾病，如精神分裂症，是一种复杂的疾病，神经生物学原因不明确。大规模的研究已经成功地确定了数百种通常会增加这些疾病风险的遗传变异，但目前尚不清楚它们运作的精确分子和细胞机制。有强有力的证据表明，许多这些遗传变异通过改变大脑发育过程中基因表达的水平来增加这些疾病的风险。在这个项目中，我们将使用尖端技术来识别影响产前人脑单个细胞群中基因表达的遗传变异。然后，我们将把这些发现与精神疾病的遗传数据联系起来，以确定介导这些疾病风险的细胞特异性基因表达变化。这些研究将促进我们对导致重大精神疾病易感性的分子和细胞机制的理解，通过这些机制可以开发出更好的治疗方法。

Mental illnesses, such as schizophrenia, are complex disorders with poorly defined neurobiological causes. Large-scale studies have been successful in identifying hundreds of genetic variants that commonly increase risk for these conditions, but the precise molecular and cellular mechanisms by which they operate are currently unclear. There is strong evidence that many of these genetic variants confer risk for these disorders by altering the level at which genes are expressed during brain development. In this project, we will use cutting-edge technology to identify genetic variants affecting gene expression in individual cell populations of the prenatal human brain. We will then link these findings with genetic data for mental illnesses to identify cell-specific gene expression changes that mediate risk for these conditions. These studies will advance our understanding of the molecular and cellular mechanisms conferring susceptibility to major mental illnesses, through which improved treatments can be developed.