Single nucleotide polymorphisms (SNPs) within GABA receptors, and several other candidate genes, are likely contributors in susceptibility to the development of alcohol dependence (Dick & Foroud, 2003). Similar to other psychiatric diseases, alcoholism is influenced by multiple genes with low-to-moderate effect (Sullivan, Daly, & O’Donovan, 2012). Polygenic factors can account for 40–60% of the risk for developing alcohol dependence (Schuckit, 2009); however, SNPs associated with disease usually reside within noncoding regions. Surveying the alcoholic transcriptome for genetic variants further corroborates this assertion (Fig. 11.11). The largest percentage of detected variants is located with sequencing reads mapped to intronic regions, followed by areas located up- or downstream of coding elements and intergenic regions. Introns are typically removed through RNA splicing events, but may be retained within individual isoforms harboring cis-acting SNPs controlling their expression (Dieter & Estus, 2010). High-throughput sequencing of human populations, as well as other model systems, is beginning to pinpoint numerous sites of nucleotide variation, that regardless of genomic loci, are capable of gene, alternative splicing, and downstream expression (Gerstein et al., 2010; Graveley et al., 2011; Lappalainen
