Given that our data suggest de novo CNVs are highly enriched for pathogenic loci, we sought evidence for convergence of de novo events onto specific biological pathways using a hypothesis-led, systems biology approach. Many of the CNVs robustly implicated in schizophrenia are also implicated in neurodevelopmental disorders in which cognitive impairment is common.39, 40, 41 Moreover, as discussed in the Introduction, it has been hypothesised that schizophrenia CNVs are enriched for genes encoding proteins associated with synaptic function. Our findings of apparent convergence of de novo CNVs onto genes encoding MAGUK proteins broadly support this synaptic hypothesis and suggested that more refined examination of synaptic genes is warranted.
