Aiming to localise more specifically the source of the PSD gene-set enrichment, we tested gene sets encoding PSD components (Table 2 and Figure 3). Activity-regulated cytoskeleton-associated protein (ARC; P=3.78 × 10−8), N-methyl-D-aspartate receptor (NMDAR; P=4.24 × 10−6) and PSD-95 complex (P=1.17 × 10−5) genes were highly significantly enriched among the de novos. However, conditional analyses revealed that the relatively small ARC and NMDAR sets explained both the PSD (conditional PPSD=0.231) and PSD-95 (conditional PPSD-95=0.603) enrichments but that the enrichments in ARC and NMDAR were partially independent of each other (conditional P=2.17 × 10−4 and P=0.019, respectively) (Supplementary Section 13). ARC and NMDAR sets also explained most of the enrichment for de novos in ‘the synapse', this GO category being only marginally enriched (P=0.017) after those genes were removed (Supplementary Section 11 and Supplementary Table S5). After removal of members of ARC and NMDAR sets, none of the subcategories comprising the synapse was significantly enriched except for ‘synaptic vesicle membrane' (P=4.22 × 10−4). These findings suggest enrichments in the PSD, and the great majority of that in the synapse GO gene
