This study adds to an accumulating body of evidence from human and animal genetic studies implicating disruption of synaptic processes in schizophrenia.45 By identifying an unprecedentedly large number of de novo CNVs in schizophrenia and demonstrating that these are likely to be highly enriched for pathogenic events, we have added substantially to the evidence implicating synaptic processes in schizophrenia. As well as implicating a set of functionally related synaptic proteins (EHMT1, DLG2, DLG1 and DLGAP1) we have identified a sufficient number of schizophrenia-enriched loci to identify potential points on convergence on specific synaptic complexes. Using gene sets that have been systematically annotated from individual, high-quality proteomic data sets and multiple analytic approaches carefully controlled for biases, we not only provide strong evidence for the importance of synaptic proteins, but also provide novel convergent support for the involvement of NMDAR, and to a lesser extent ARC protein, complexes in the aetiology and pathogenesis of the disorder, both of which are involved in NMDA signal transduction. NMDA receptor signalling regulates induction of multiple forms of synaptic plasticity,46 with local synthesis of ARC
