Leveraging network properties for the pairwise relationship among genes allows for the identification of functionally relevant candidates in neuroplasticity and disease 49, 50. Although modules within Group1 share similar expression patterns, the individual gene sets may also contribute to differing states of disease progression. We hypothesized that identifying genes within central positions (i.e., hub genes) of the alcohol-perturbed modules would distinguish major, yet underappreciated, participants in the neurobiology of human alcohol consumption. GM15, GM20, GM25, and GM31 were restricted to the top ten percent of connected genes, highlighting the primary contributors within the network that are associated with lifetime alcohol consumption (Fig. 3). Among the most central elements are glutamatergic and GABAergic receptors (GABRA3, GABBR1, GABBR2, GRIA1, and GRIN2B), two neurotransmitter systems widely recognized to affect alcohol-induced behaviors 51. In addition, a number of candidates within these networks represent novel determinants of alcohol dependence. Hub genes within these molecular networks conceivably act across species as 25/104 the core genes coincide with the aforementioned meta-analysis of alcohol drinking behavior in mice 45. Probing specific targets across species may highlight unknown pathways
