Among the most highly connected hubs within ErGeN3 were a number of genes that have been previously implicated in modulating level of response to ethanol or susceptibility to alcohol dependence (Figure 6), including Kcnma1 and Gsk3β. Kcnma1 is a large conductance potassium channel whose activity is directly affected by ethanol [49]. Gsk3β, is a serine/threonine kinase that participates in the WNT signaling pathway and is an important modulator of ethanol-induced neurotoxicity in both mice [50] and Drosophila [51]. These findings on Kcnma1 and Gsk3β serve to validate our network analysis approach, identifying these and other hub genes (Figure 6) as potentially important modulators of ethanol phenotypes.
