Mindful of the fact that more than half of genes harboring de novo damaging variants in our study may not be true risk genes, we consider our pathway and network analyses as exploratory at this stage. Nevertheless, we see preliminary evidence that genes identified by de novo damaging variants in OCD are functionally connected to a greater degree than expected by chance (Figure S6, Table S7). Furthermore, these genes may be enriched in immunological and complement system canonical pathways (FDR 0.13; Table S8), consistent with our pilot study of exome sequencing in 20 OCD trios (31). More robust enrichment is seen for sodium ion homeostasis processes (FDR~10−7) and cancer-related disease pathways (FDR~10−8–10−9). These analyses should be viewed as preliminary and should be repeated as more high-confidence OCD risk genes are identified.
