A COGA GWAS study in families densely affected with AUD has shown genome‐wide association with noncoding SNPs and a highly correlated imputed synonymous SNP in the KCNJ6 gene and theta brain oscillations during a task measuring selective attention and response inhibition, a neural phenotype also associated with AUD. 55 A synonymous (rs702859) and two noncoding (rs702860 and rs2835872) SNPs were shown to affect neurodevelopmental trajectories of event‐related theta oscillations with age and sex‐specific effects 56 and to be associated with theta power during reward processing in COGA's prospective study of adolescents and young adults (Figure 4, Panels A and B) 57 (also see 3. Brain function in this issue). KCNJ6 encodes the G protein‐gated inwardly rectifying potassium channel subunit 2 (GIRK2) and plays a critical role in regulating the excitability of a variety of neuronal cell types. 58 In rodent studies, GIRK channels are implicated in alcohol‐related behaviors. 58 In addition, GIRK channels can be directly potentiated by alcohol through interaction with a hydrophobic pocket in the channel. 59 It was unclear, however, how the noncoding KCNJ6 variants might affect the GIRK channels and neuronal function and relate to AUD phenotype.
