Among the novel loci, we highlight GRIA1 and GABRA1, encoding a glutamate ionotropic AMPA type 1 receptor subunit (GluA1) and a GABA receptor subunit (α1), respectively (Supplementary Table S2). The two genes also showed significant imputed differential expression in the DLPFC (Supplementary Table S9) in our TWAS77-79. Our pathway analysis reinforced previous reports12,14,25 and extended the enrichment of glutamatergic and GABAergic synapses and functions, further indicating that glutamatergic and GABAergic dysfunctions are key etiologic components in depression. Along with the observed enrichment of GABAergic cell-types already present during the prenatal stage, this supports the accumulating multidisciplinary evidence that implicate excitatory/inhibitory imbalance with depression80 and other psychiatric disorders81-84.
