Applying stem cells and CRISPR engineering to uncover the etiology of schizophrenia

Schizophrenia is a highly heritable, polygenic disorder. A growing list of common genetic variants have been associated with schizophrenia; there is a clear need to understand the role of these risk factors in the etiology of disease. The majority of these variants occur in noncoding regions of the genome and are thought to regulate the expression of one or more genes in a cell type–specific fashion. Recent advances in stem cell biology and molecular genetics have resulted in two invaluable advances: hiPSC technology makes possible the generation of donor-specific disease-relevant neural cell types, whereas CRISPR-based techniques can be applied to manipulate individual variants and/or their gene targets. New multiplexed gene manipulation and CRISPR screening techniques show great promise toward dissecting the complex interactions between the myriad disease-associated variants. This review outlines key advances in hiPSC and CRISPR technology, describing their applications and future potential in the field of schizophrenia research.