A number of isolated model system approaches have implicated ion channels 39 and signaling networks 40 in the neurobiology of alcohol; however, such studies may overlook small responses or fail to capture widespread heterogeneous molecular effects in humans 41. Our results demonstrate a markedly orchestrated network of these genes in human PFC related to the degree of lifetime alcohol consumption, providing a framework for deciphering multiple genes in the context of a specific phenotypic trait of alcohol dependence. Molecular function for these networks spans multiple dimensions, but tie together several relevant biological processes of alcohol exposure. Glutamate receptor activity (P = 3.86 e-05), a known system underlying the PFC circuitry of compulsive behavior in addiction 42 and a direct pharmacological target of alcohol 43, is just one of several functional categories enriched within GMs associated with lifetime alcohol consumption.
