Concentrating on the top ten percent of genes, within Group1 of the upper quartile, related to lifetime alcohol consumption identified three high-confidence genes (SCN4B, SYT13, and TBC1D9) in common between mice and humans (Fig. 3). The voltage-gated sodium channel is a putative quantitative trait gene (QTG) for alcohol drinking behavior 45, 55. Serving as an auxiliary partner to sodium channel alpha subunits within neurons, SCN4B can override the effects of other beta subunits 56, modify sodium channel firing rates 57, and structurally alter neuronal projections 58. Currently there is only one recognized isoform of SCN4B in rodents; however, there are three coding isoforms of SCN4B in humans. Only the shortest coding variant (NM_001142349) is significantly correlated to alcohol consumption (Fig. 4). WGCNA of alternatively spliced transcripts closely mirrors pairwise gene expression profiles for biological function (Table S3, Fig. S7); NM_001142349 being an appreciable phenotypic focal point within the network that is distinct from the other two coding isoforms of SCN4B. Differentially spliced transcripts expressed alongside NM_001142349 included NM_014191 (SCN8A) (Fig. S7), a sodium channel alpha subunit expressed within cortical nodes
