Aiming to identify novel candidate CNV loci for schizophrenia, and to illuminate aspects of the pathophysiology of the disorder through gene-set enrichment analyses, we have conducted the largest analysis of de novo CNVs in schizophrenia to date. Although not every observed case de novo CNV is likely to be pathogenic, the hypothesis that a substantial proportion of them are likely to be so is supported by several observations. First, eight of the de novos occurred at already known schizophrenia CNV loci (Table 1, marked with footnote ‘a'). Second, even after conservatively excluding those known loci, CNVs at the loci affected by case de novos occurred twice as frequently in cases in a meta-analysis of the largest available case–control CNV data sets. This elevation is much higher than the overall increase in CNV burden in cases in the large published studies.2, 4 Third, in the trios sample, the rate of de novo CNVs was more than twice that observed in other control samples (Supplementary Table S3), suggesting that at least 50% of the case de novos are relevant to the pathophysiology of schizophrenia.
