Based on the primary analysis using DAVID, eight functional categories were enriched among de novo CNVs in SCZ (p < 0.05). Three were also found to be enriched based on permutation tests of de novo CNVs in cases and controls, including “neural tube development,” “hindbrain development,” and “response to ethanol” (Table 4). Genes involved in neurodevelopment were not enriched among de novo CNVs in BD (Table 5) or in controls (Table S7). We then extended our analysis of schizophrenia to a large independent data set of rare (>100 kb) CNVs from 8,290 cases and 7,431 controls. Eight categories were tested in the case-control sample using the PLINK-CNV parametric test, and two categories, “synapse” and “Kelch-type beta propeller,” were significantly enriched among rare variants in cases (Table 4). The case-control data set did not provide significant support for an enrichment of genes related to neural tube development or hindbrain development. While the strength of evidence supporting specific pathways differs between data sets, we do find evidence consistent with our earlier observations that there is an enrichment of “neurodevelopmental” and “synaptic” genes among rare CNVs in SCZ (Walsh et al., 2008).
