The results presented here also strongly implicate gene networks that regulate synaptic function, which have been identified in previous studies, and this was found here across all disorders. A recent gene-set enrichment analysis of de novo CNVs in schizophrenia found synaptic processes to be highly enriched.63 Specifically postsynaptic gene networks, including the NMDAR complex, were significant. A pathway analysis of rare de novo CNVs in ASD was recently conducted using a network-based analysis of genetic associations (NETBAG).64 Enriched gene networks identified processes related to actin network dynamics and reorganization, synaptogenesis, axonogenesis, cell–cell adhesion, small GTPase signaling, and neurite development. One GWAS ASD study conducted a pathway analysis of rare CNVs (deletions only as they were significant over controls) and identified cell proliferation, cell projection, cell motility, GTPase/Ras signaling, and kinase activity/regulation.36 The same study analyzed ASD/ID genes and found enriched processes related to microtubule cytoskeleton, glycosylation, and central nervous system (CNS) development/adhesion. Our results support these findings and demonstrate that cytoskeleton organization may be more associated with the ID phenotype.
