Our second genome-wide significant locus was tagged by rs11710497, located within GABA transporter 1—SLC6A1 (solute carrier family 6 (neurotransmitter transporter, GABA), member 1). Given that alcohol functions primarily through binding to GABA receptors, and that this gene encodes protein GAT-1, which removes GABA from the synaptic cleft, there is a notably high prior probability of this being a true discovery. Furthermore, while the two genome-wide significant/suggestive hits were in intronic regions, they tag strongly associated exonic variants in SLC6A1. Although the network biology of the gene suggests obvious links to alcohol consumption, there has been surprisingly little research studying this relationship. Conversely, studies have implicated the gene in anxiety disorders and ADHD (e.g., Lasky-Su et al., 2008; Thoeringer et al., 2010; Thoeringer et al., 2009). This finding should focus future research on the study of SLC6A1 variants in alcohol abuse and other psychiatric phenotypes related to cortical excitability/inhibition.
