in intronic regions (Kang et al., 2012). KCNJ6 encodes the G protein-gated inwardly rectifying potassium channel GIRK2, which plays an important role in regulating neuronal excitability by stabilizing the membrane potential (Lüscher and Slesinger, 2010). KCNJ6 is expressed in cholinergic, GABAergic, glutamatergic, and, most prominently, dopaminergic neurons (del Burgo et al., 2008). Additionally, GIRK2 has been shown to be directly activated by alcohol (Aryal et al., 2009; Bodhinathan and Slesinger, 2014; Glaaser and Slesinger, 2017). Eleven significant SNPs in KCNJ6 were also identified in an association study between adult drinking, adolescent drinking, and early life stress interactions (Clarke et al., 2011). The variant SNPs identified in KCNJ6 do not result in amino acid changes, suggesting potential differences in gene expression or distal regulatory effects on other genes. The theta ERO differences in AUD patients suggest potential differences in neuronal activity, which can be investigated in vitro, providing a phenotype to overlay the complex genetic interactions. Identification of common cellular phenotypes either at baseline or upon treatment with ethanol could identify targets for pharmacotherapy to normalize divergences in electrophysiological activity.
