All of the currently known risk CNVs are rare (control frequencies typically <0.001) and confer substantial effects on risk (odds ratios 3–30). The known risk CNVs occur in 2–3% of cases, but it is likely that many other risk CNV loci remain to be identified. Most schizophrenia-associated CNVs span multiple genes, limiting our ability to make strong inferences regarding pathogenesis. Important exceptions are deletions of NRXN1, encoding the presynaptic neuronal cell adhesion molecule neurexin 1,11, 15 pointing to the importance of as yet unspecified abnormalities of synaptic function in the disorder. Also, obscuring mechanistic insights from the CNV data are that most reported CNVs occurring in cases are too rare to allow clear demonstration of association statistically. One way to circumvent this is to test whether particular functionally related groups or sets of genes are enriched among case CNVs, rather than trying to interpret the results from individual CNVs. A limitation of this approach is that the enrichment of CNVs seen in case–control studies is modest;2 indeed, one large study has reported no overall excess of CNVs in cases at
