The strongest association we observed resides near KCNJ9; the frequency of the implicated imputed allele was very low (MAF = 0.002), suggesting the need for caution. The power to detect a significant association at this allele frequency was of XX. KCNJ9 encodes one of the G protein-activated inwardly rectifying K+ channels (GIRK3), which are expressed in the brain (Koyrakh et al. 2008), and can be directly activated by ethanol (Herman et al. 2015), even at low concentrations. In humans, two linkage studies have mapped this region for AUD (Hill et al. 2004), age of onset of drinking, harm avoidance, and novelty seeking (Dick et al. 2002). Additionally, DNA methylation levels of CpG in the promoter region of the GRIK3 gene showed altered expression in postmortem prefrontal cortex tissue of male alcoholics (Wang, Xu, Zhao, Gelernter & Zhang 2016). In mice, Kcnj9 also harbors a QTL for a variety of alcohol-related behaviors, including: ethanol preference (Tarantino, McClearn, Rodriguez & Plomin 1998), ethanol aversion (Risinger & Cunningham 1998), acute sensitivity to ethanol (Tipps, Raybuck, Kozell, Lattal & Buck 2016), and hypersensitivity to
