Enzyme-related genes are most numerous group, with PRKG1, CAMK1D, CHN2, FHIT and SERPINA1 providing th most significant comvergent observations. PRKG1, the cyclic-G dependent protein kinase 1, and FHIT, the fragile histone triad gene that represents a diadenosinase, each display clustered, nominally-positive SNPs in several of these studies in ways that make them especially unlikely to represent chance findings. PRKG1 is expressed in brain and in hippocampal, cerebellar and other neurons [260]. Nitric oxide dramatically modulates brain cGMP systems; PRKG1 thus provides a major target for the products of nitric oxide synthases (NOS). Mnemonic and addictive functions can each be altered by changes in cGMP-dependent protein kinase and/or NOS [261]. Identification of potent imidazopyridine PRKG inhibitors for use in lower species could well provide leads for development of similar compounds for use in humans [262].
