The Manhattan and quantile-quantile (QQ) plots for AUDIT are shown in Figure 2 and Supplementary Figure 4, respectively. The most significant association was at rs182344113, located on chromosome 1 (P = 2.10 × 10−7; β = 0.168, SE = 0.03; MAF = 0.002; Supplementary Fig. 1). The association was in an intergenic region of the gene PIGM, and near KCNJ9 (GIRK3), which has been implicated in preclinical models of ethanol sensitivity. G-protein–gated inwardly rectifying potassium (GIRK) channels, which are coupled to GABA-B receptors, can be activated by ethanol (Aryal, Dvir, Choe & Slesinger 2009; Bodhinathan & Slesinger 2013). Interestingly, Kcnj9 knock-out mice exhibit excessive alcohol drinking (Dere et al. 2015).
