Co-analysis of human GWA studies and ErGeN hub genes may provide a bidirectional validation for such genes, even leading to candidates for therapeutic targeting. However, taken out of context, such single genes still do not define the mechanisms underlying cellular, neural network or behavioral responses to ethanol, which remains our chief objective in identifying and dissecting these gene networks. Direct validation of hub genes, in terms of both gene network regulation and phenotypic responses, are required to fully understand the role of these ethanol-responsive networks in complex behavioral responses. Ongoing studies in our laboratory seek to adapt and extend this approach, through genetic manipulation of ErGeN hub genes, in order to observe downstream effects on the original ethanol-responsive network as well as the network-associated ethanol behavioral phenotypes. Such validation of network-derived candidates could provide a novel approach to future pharmacotherapies for AUD, directed against regulation of a gene network rather than function of a single protein.
