Schizophrenia (SCZ), affecting roughly 0.7% of adults, is a severe psychiatric disorder characterized by abnormalities in thought and cognition1. Despite a century of evidence establishing its genetic basis, only recently have specific genetic risk factors been conclusively identified, including rare copy number variants2 and >100 common variants3. However, there is not a one-to-one Mendelian mapping between these SCZ risk alleles and diagnosis. Instead, SCZ is truly complex and appears to result from a myriad of genetic variants exerting small effects on disease risk4,5, conforming closely to a classical polygenic model. The available data are incomplete but implicate synaptic components, including calcium channel subunits and post-synaptic elements5–7. A consequence of polygenic inheritance is that the small effect sizes of individual variants complicate characterization of the biological processes they influence, both at the level of particular genes and pathways.
