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To identify new schizophrenia genes by investigating copy number variation (CNV) across the genome.

The researchers performed a genome-wide scan in 802 patients and 742 controls for CNVs. This discovery phase was then replicated in a further 7500 patients and 6700 controls.

In the discovery phase, 114 CNVs were identified. Following the second stage, four of these regions were shown to be associated with a further four regions showing nominal association. Three of the four associated regions contain well-documented risk loci for schizophrenia but the region on chromosome 7 had not previously been implicated. This fourth region contained microduplications affecting the VIPR2 gene, which codes for a protein that is expressed in the limbic system of the brain.

The identification of VIPR2 by this study supports the idea that schizophrenia is caused in some patients by dysregulation of processes affecting the cognitive processing of learning and memory, and includes involvement of certain brain regions such as the hippocampus and amygdala. The authors suggest that significant potential exists for the development of therapeutics targeting this receptor with several existing inhibitors.

This study used a large two-stage genome-wide approach to identify rare CNVs in regions previously associated with schizophrenia, as well as a new region on chromosome 7 containing the VIPR2 gene. This gene is a very good biological candidate and this region has also been implicated in other neurodevelopmental disorders such as autism, perhaps suggesting a wider involvement in neurological disease processes. However, it should be noted that this microduplication was very rare, occurring in less than 0.5% of the 8,000 schizophrenia patients tested in this study. This highlights the need for large scale collaborative efforts to identify such variants and also adds to the growing list of rare variants implicated in common complex conditions.