The results are consistent with the genome-wide enrichment tests pointing to postsynaptic pathology. However, many prioritised genes had additional locations suggesting that presynaptic pathology may also be involved. The encoded proteins map to 16 unique biological terms in the hierarchy (Supplementary Table 19), but there are specific themes. Multiple genes encode receptors and ion channels, including voltage-gated calcium and chloride channels (CACNA1C, CLCN3), metabotropic receptors (glutamate (GRM1) and GABA (GABBR2)), and the ligand-gated NMDA receptor subunit (GRIN2A). Others involve proteins playing a role in endocytosis (SNAP91), synaptic organisation and differentiation (DLGAP2, LRRC4B, GPM6A, PAK6), including PTPRD a receptor protein tyrosine phosphatase presynaptic organizer that trans‐synaptically interacts with multiple postsynaptic cell adhesion molecules (e.g. IL1RAPL1), and modulation of chemical transmission (MAPK3, DCC, CLCN3, DLGAP2). The diversity of synaptic proteins identified in this study suggests multiple functional interactions of schizophrenia risk converging on synapses. It remains to be determined whether these interactions occur at a limited set of specific synapse types, or whether the diversity points to multiple types in different brain regions.
