In addition to identifying hub genes as leading candidates for future verification studies, our genetic dissection of ethanol-responsive gene networks also produced clues regarding the mechanisms underlying ethanol network responses. Identification of chromosomal hot spots linked to ethanol responses for entire gene networks provides genetic evidence for hubs influencing the response of ErGeN's and expands our understanding of brain molecular signaling events responding to ethanol. For example, the sodium channel Scn1b was a hub gene in ErGeN1, showed robust ethanol-responsiveness, had a highly significant cis-eQTL and also was a strong candidate for regulating a trans-band of ErGeN3 mapping to exactly the location of Scn1b. Scn1b codes for a regulatory subunit of sodium channels which are crucial to action potential propagation. Ethanol has been shown previously to inhibit sodium channel function [86]. This data suggests that Scn1b and other such potential regulators of ethanol-responsive trans-bands may be key modulators for extensive portions of the overall ethanol responsome.
