There were interesting distinctions among brain disorders. For example, all brain disorders showed postsynaptic associations, while a selected set of disorders (ADHD, SCZ, MDD, and MS) also exhibited presynaptic associations. Further, while the majority of brain disorders displayed enrichment in glutamatergic signaling, ASD, SCZ, and ALS displayed enrichment in GABAergic signaling. ASD-associated genes were enriched for acetylcholinergic and serotonergic signaling, reflecting known biology of ASD20,21. SCZ and BD-associated genes were also enriched for acetylcholinergic signaling, supporting previous studies that altered cholinergic signaling contributes to SCZ and BD pathogenesis4,22. MS-associated genes were enriched for dopaminergic signaling, disruption of which has been associated with immune malfunction in MS23. These results collectively highlight synaptic dysfunction in brain disorders, albeit we could detect distinctions among disorders based on neurotransmitters and pre/post synaptic associations.
