Another well-replicated locus associated with both alcohol consumption and AUD is the region containing the glucokinase receptor (GCKR) gene, whose product is a regulatory protein that is produced by hepatocytes and is involved in the cellular trafficking of glucokinase. A nonsynonymous SNP in GCKR, rs1260326, was robustly associated with alcohol consumption in the MVP, UKB and 23andMe samples (Table 1). Intriguingly, rs1260326 has also been previously associated with multiple metabolic traits, including diabetes, obesity and liver disease (30, 31). Given that alcohol consumption is strongly associated with both metabolic and lipid profiles (e.g. 25, 32, 33), it is not clear whether the association with rs1260326 pinpoints a pleiotropic process central to metabolic traits, or whether alcohol causally impacts glucose metabolism and lipid levels, in part via GCKR. A recent study characterized the effects of alcohol in neural cell cultures derived from induced pluripotent stem cells (iPSCs) and found that genes down-regulated upon alcohol exposure were involved in cholesterol homeostasis in the brain (34). These findings could suggest that AUD has both psychiatric and metabolic components, a theme that has also
