To identify the biological pathways that are influenced by the putative genes associated with depression, gene-set analyses were performed using MAGMA 14. This method identifies the genes involved in each biological pathway and assesses whether there is evidence of enrichment for each pathway in depression using the P-values of each gene. We identified 14 significant putative gene-sets (Pcorrected < 0.05) for depression (Table 3) using data from the Gene Ontology Consortium. Eight of these gene-sets were cellular components (areas where the genes were active) and were located in the nervous system: GO_POSTSYNAPSE, GO_SYNAPSE, GO_NEURON_SPINE, GO_EXCITATORY_SYNAPSE, GO_SYNAPSE_PART, GO_NEURON_PROJECTION, GO_NEURON_PART, and GO_DENDRITE. The cellular component gene-sets intimate a role in synapse function and excitatory mechanisms. The other six associated gene-sets were biological processes: GO_BEHAVIOR, CO_COGNITION, GO_MODULATION_OF_SYNAPTIC_TRANSMISSION, GO_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GO_MODULATION_OF_SYNAPTIC_PLASTICITY, and GO_SINGLE_ORGANISM_BEHAVIOR. The gene overlap between these gene-sets (Supplementary Table 10) suggests that the gene-sets generally fall within two clusters. One gene-set cluster typically relates to synaptic structure and activity while the other gene-set cluster relates to the response or behaviour to stimuli. We also identified a significant gene-set (P = 3.87 × 10-5) containing somatosensory pyramidal neurons using brain cell-type data from Skene, et al. 15 (Table 3).
