Alternative splicing of transcripts occurs for ~95% of multiexon genes in humans 73 and produces substantial functional diversity and flexibility in complex phenotypes. RNA-Seq has the ability to delineate human-specific gene isoforms relevant to neurobiology and disease. Few studies to date have conducted large-scale studies on alternative splicing for alcohol consumption. Lack of existing studies on alternative splicing for alcohol use disorders across populations limits the ability to compare the results herein. The shortest coding version of the reported QTG SCN4B is one example significantly correlated to lifetime consumption and is part of a transcriptional network that may alter neurophysiological responses to alcohol. Although further experiments are necessary to probe molecular interactions with alcohol and yet unforeseen physiology of splice variants, our analysis provides evidence within a network-based infrastructure involving multiple adjoining isoforms for alcohol dependence. For example, activity of SCN8A transcripts, the density of which is maintained by the composition of white-matter 74, may be altered by interaction with SCN4B isoforms and in turn collectively affect neuronal properties amongst a network of receptor-mediated systems. RNA-Seq studies are poised to
