For the global analysis, we noted that several of the enriched GO gene set pathways had a high proportion of overlapping genes. We leveraged this overlap to explore the links between enriched gene sets and draw broader conclusions about the nature of transcription alterations in OCD. Hierarchical clustering revealed four distinct sub-networks (clusters) of gene sets (Fig. 2). Of note, cluster 1 contained 16 gene sets that could be attributed to the synapse (Fig. 2). We also tabulated the number of enriched gene sets with either upregulated or downregulated DEG in OCD subjects versus unaffected comparison subjects (Table S3). Because our previous qPCR work36 identified lower levels of several synaptic transcripts within the OFC and striatum of OCD subjects compared to unaffected comparison subjects, we sought to determine whether the genes identified in these synaptic gene sets contained more downregulated genes than other clusters. For the 16 synaptic gene sets identified in cluster 1, the fraction of genes that were downregulated in each set was significantly higher than that for the remaining 16 gene sets (mean fraction of downregulated genes
