Both the Gene Network and the DEPICT analyses separately point to a role for glutamate and GABA neurotransmitters, which are the main excitatory and inhibitory neurotransmitters in the brain, respectively34 (Fig. 3a and Supplementary Tables 18 and 19). To our knowledge, with the exception of a recent study35 prioritizing a much larger number of genes and pathways, no published large-scale GWAS of cognition, personality, or neuropsychiatric phenotypes has pointed to clear roles both for glutamate and GABA (although glutamatergic neurotransmission has been implicated in recent GWAS of schizophrenia36 and major depression37). Our results suggest that the balance between excitatory and inhibitory neurotransmission may contribute to variation in general risk tolerance across individuals.
