Update on the genetic architecture of schizophrenia

A long-established hypothesis is that schizophrenia has a strong genetic component. In the early 1990s, the first genetic variant that substantially increases risk for psychosis was identified. Since this initial reporting of deletions in the chromosomal region 22q11.2, nearly two decades passed until substantial insights into schizophrenia's genetic architecture were gained. Schizophrenia is a polygenic disorder and genetic risk is conferred by both common and rare alleles distributed across the genome. A small number of rare, deleterious copy number variants (CNVs) are associated with moderate to substantial increases in individual risk to schizophrenia. These deletions and duplications are also associated with a range of neurodevelopmental disorders. The diagnostic investigation of CNVs in patients with schizophrenia is likely to represent one of the first examples of genetic testing in clinical psychiatry. The prerequisites for this are currently being defined.