Clinical genetics of schizophrenia and related neuropsychiatric disorders

Abstract

Rare structural variants have turned out to be the long sought for genetic variants of (relatively) high effect size for schizophrenia. Delineating the 22q11.2 microdeletion as the first molecular subtype of schizophrenia was a milestone in schizophrenia research, foreshadowing a more general role for rare copy number variation (CNV) in schizophrenia. The 22q11.2 microdeletion has a high effect size – one in every four individuals born with this deletion develops schizophrenia – and a relatively high prevalence for a rare condition. Discovery of this human genetic high-risk model for schizophrenia has shown how genetics can change clinical management, and also provide new opportunities for animal and cellular models. Further new findings indicate a role for tandem repeat expansion, other less complex rare variants, and collective background effects of common variants in the genetics of schizophrenia. Thus, the genetic architecture of schizophrenia is taking shape, with further advances on the horizon.