To investigate the connectivity among the 25 depression causal proteins from the meta-analysis, we used GeNets, a web platform for network-based genomic analyses24. We found two protein communities based on protein-protein interaction (PPI; Figure 2). A community is a set of proteins that are more connected to one another than they are to other groups of proteins24. The first community included CSE1L, CTNND1, SLC25A12, and PSMB4, and the second community LYRM4 and GMPPB proteins (Figure 2). GeNets also enables gene set enrichment analysis on genes within a PPI network using the canonical pathways from gene sets in the MSigDB25. We found that these 25 causal genes were enriched for genes involved in amyotrophic lateral sclerosis (CCS, PPP3CC), calcium signaling (PPP3CC, P2RX7, ADCY3), dilated cardiomyopathy (CACNA2D2, ADCY3), oocyte meiosis (ADCY3, PPP3CC) and metabolism of amino acids and derivatives (HIBADH, PSMB4; Figure 2).
