title: A KCNJ6 gene polymorphism modulates theta oscillations during reward processing.
abstract: 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 17-25years (800 males and 801 females) from high-dense alcoholism families as well as control families of the COGA prospective study. Theta ERO power (3.5-7.5Hz, 200-500ms 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).
authors.affiliation: Henri Begleiter Neurodynamics Lab, SUNY Downstate Medical Center, Brooklyn, NY, USA. Electronic address: kam@hbnl.downstate.edu.
authors.forename: Chella
authors.initials: C
authors.lastname: Kamarajan
authors.affiliation: Henri Begleiter Neurodynamics Lab, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Ashwini K
authors.initials: AK
authors.lastname: Pandey
authors.affiliation: Henri Begleiter Neurodynamics Lab, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Chorlian
authors.affiliation: Henri Begleiter Neurodynamics Lab, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Niklas
authors.initials: N
authors.lastname: Manz
authors.affiliation: Henri Begleiter Neurodynamics Lab, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Arthur T
authors.initials: AT
authors.lastname: Stimus
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Wetherill
authors.affiliation: University of California San Diego Medical Center, San Diego, CA, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Schuckit
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jen-Chyong
authors.initials: JC
authors.lastname: Wang
authors.affiliation: University of Iowa, Iowa City, IA, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kuperman
authors.affiliation: University of Iowa, Iowa City, IA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kramer
authors.affiliation: The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Tischfield
authors.affiliation: Henri Begleiter Neurodynamics Lab, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
mesh_terms: D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000235:genetics / Q000503:physiopathology; D000704:Analysis of Variance; D001931:Brain Mapping; D004569:Electroencephalography; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D005715:Gambling / Q000523:psychology; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D010775:Photic Stimulation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012201:Reward; D013826:Theta Rhythm / Q000235:genetics*; D055815:Young Adult
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C094401:KCNJ6 protein, human
keywords: Alcoholism; COGA; Event-related oscillations (EROs); GIRK2; KCNJ6; Monetary gambling task; Reward processing; Theta power