Experimental Model Systems for Rare and Common Variants

Excerpt

Resolving the target genes, pathways, cellular phenotypes, and circuit functions impacted by the hundreds of genomic loci significantly associated with psychiatric disorders is a major challenge. Applications of genomic engineering in human-induced pluripotent stem cells (hiPSCs) and mice are widely used to study the impact of psychiatric risk variants within defined cell types of the brain. As the scale and scope of functional genomic studies expands, so must our ability to resolve the complex interplay of the many risk variants linked to psychiatric disorders. Here we discuss the current state of the field, with particular emphasis on hiPSC and mouse models, which have facilitated efforts to understand the pathophysiology of psychiatric disorders and translate genetic findings into disease-relevant biology in the service of advancing diagnostics and therapeutic development.