Cell-specific gene regulation in the developing human brain and genetic risk for neuropsychiatric disorders

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Large-scale genetic studies have identified hundreds of regions of the human genome that commonly influence susceptibility to mental illnesses such as schizophrenia. The great majority of these risk variants are located in areas of the genome that do not encode proteins and are therefore thought to instead affect gene expression (i.e. the amount of that gene that the cell produces as RNA / protein). Recent studies indicate that many of these risk variants are active in the prenatal human brain, but the cells involved are unknown. We will use cutting-edge technology to determine the constituent cell types of 5 regions of the developing human brain and the genomic sites controlling gene expression within them. We will integrate these data with results from large genetic studies to delineate cell types of the prenatal brain that mediate genetic risk for psychiatric disorders. These studies will greatly advance our understanding of the cellular basis of major mental illnesses, which will promote improved treatments for these conditions.