A KCNJ6 gene polymorphism modulates theta oscillations during reward processing

- The effects of a KCNJ6 gene variant, rs702859, on theta oscillations during reward processing was examined
- Theta power increased based on the minor allele dose (GG > AG > AA) in posterior regions in both loss and gain conditions
- The minor allele genotypes (GG and AG) had less frontalization than the AA genotype, suggesting a delay in brain maturation
- Evidence from studies suggests that KCNJ6 may be a promising therapeutic target for alcoholism and related disorders
- Functional studies on the KCNJ6 system may shed more light on neurogenetic mechanisms underlying cognitive (dys)functioning

Event related oscillations (EROs) are heritable measures of neurocognitive function that have served as useful phenotype in genetic research. A recent family genome-wide association study (GWAS) by the Collaborative Study on the Genetics of Alcoholism (COGA) found that theta EROs during visual target detection were associated at genome-wide levels with several single nucleotide polymorphisms (SNPs), including a synonymous SNP, rs702859, in the KCNJ6 gene that encodes GIRK2, a G-protein inward rectifying potassium channel that regulates excitability of neuronal networks. The present study examined the effect of the KCNJ6 SNP (rs702859), previously associated with theta ERO to targets in a visual oddball task, on theta EROs during reward processing in a monetary gambling task. The participants were 1601 adolescent and young adult offspring within the age-range of 17-25 years (800 males and 801 females) from high-dense alcoholism families as well as control families of the COGA prospective study. Theta ERO power (3.5-7.5 Hz, 200-500 ms post-stimulus) was compared across genotype groups. ERO theta power at central and parietal regions increased as a function of the minor allele (A) dose in the genotype (AA > AG > GG) in both loss and gain conditions. These findings indicate that variations in the KCNJ6 SNP influence magnitude of theta oscillations at posterior loci during the evaluation of loss and gain, reflecting a genetic influence on neuronal circuits involved in reward-processing. Increased theta power as a function of minor allele dose suggests more efficient cognitive processing in those carrying the minor allele of the KCNJ6 SNPs. Future studies are needed to determine the implications of these genetic effects on posterior theta EROs as possible “protective” factors, or as indices of delays in brain maturation (i.e., lack of frontalization).