POMC encodes proopiomelanocortin which is a preproprotein that undergoes extensive, tissue-specific, post-translational enzymatic processing yielding as many as ten biologically active peptides involved in diverse cellular functions. Adrenocorticotropic hormone (ACTH) and the endogenous opiates Beta-endorphin and Met-enkephalin are the most notable peptides derived from POMC; ACTH controls the secretion of glucocorticoids from the adrenal glands and is an integral signaling peptide along the hypothalamic–pituitary–adrenal axis (HPA) with its well-known roles in regulation of the stress response. Endorphins and enkephalins are the primary endogenous ligands for mu-opioid receptors in the brain. Genetic variation in POMC, which produces ACTH and the endogenous opiate receptor ligands, therefore could have several logical functional roles in mediating the alcohol dependence phenotype because of the documented role of these peptides in stress and reward mediated behaviors (Belda et al., 2015; Charbogne et al., 2014). For example, individuals with a family history of alcoholism have lower plasma concentrations for beta-endorphin and ACTH (Gianoulakis et al., 2005), which suggests a dysfunction of the HPA-axis that may be related to genetic variation in POMC associated with alcohol dependence. In
