We used the high-confidence gene list from SNP-based fine-mapping, TWAS, and PWAS (subset of Table S8) to identify enriched synapse functions using Synaptic Gene Ontologies (SynGO).15 The 43 genes from the high-confidence gene list with SynGO annotations were compared against a background of 18,035 brain-expressed genes. We replicated earlier findings from Howard et al.,2 showing enrichment of neuron differentiation processes and postsynaptic membrane components. The current GWAS provided greatly increased specificity, implicating the cytosol, active zone membrane, calcium levels, vesicle cycle, and presynaptic endocytosis. At the post-synapse, there was enrichment of synaptic specialization, density, and receptor clustering (Tables S5A and S5B).
