Genome-wide association studies have found strong evidence for association between schizophrenia and a number of genetic variants, both common and rare.1 So far, the evidence for rare variants comes mainly from the analysis of deletions and duplications of segments of DNA known as copy number variants (CNVs). Cumulatively, as a general class, large (>100 kb) rare (<1%) CNVs occur more frequently in those with schizophrenia2, 3 than controls, and several individual CNV loci have been strongly implicated as risk factors for schizophrenia with high degrees of statistical confidence. These include deletions at 1q21.1, NRXN1, 3q29, 15q11.2, 15q13.3, 22q11.2 and duplications at VIPR2, 16p11.2, 16p13.1 and 15q11-q13.2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 Pleiotropic effects are common, the same CNV often conferring risk for a range of neurodevelopmental phenotypes including autism, mental retardation, attention deficit hyperactivity disorder and epilepsy, although interestingly, and in contrast to the findings with common risk alleles, there is little evidence that schizophrenia-associated CNVs confer risk for bipolar disorder.14
