To address central cell types mediating risk for brain disorders, we next assessed cell-type specific expression profiles of brain disorder risk genes (Methods). One striking difference between psychiatric and degenerative disorders was that psychiatric disorder-associated genes coalesced in neurons, while degenerative disorder-associated genes were highly expressed in glia (microglia for AD and MS, astrocytes for ALS and PD, Extended Data Fig. 4a). Since psychiatric disorders showed neurodevelopmental origin, we also measured cell-type specific expression profiles of psychiatric disorder-associated genes in the developing cortex and found convergence onto outer radial glia and excitatory neurons (Extended Data Fig. 4b). This selective enrichment in excitatory neurons prevailed across development, as adult neuronal expression profiles for psychiatric disorder-associated genes also indicated excitatory neuronal enrichment (Extended Data Fig. 4b).
