title: Family-based genome-wide association study of frontal θ oscillations identifies potassium channel gene KCNJ6.
abstract: Event-related oscillations (EROs) represent highly heritable neuroelectric correlates of cognitive processes that manifest deficits in alcoholics and in offspring at high risk to develop alcoholism. Theta ERO to targets in the visual oddball task has been shown to be an endophenotype for alcoholism. A family-based genome-wide association study was performed for the frontal theta ERO phenotype using 634 583 autosomal single nucleotide polymorphisms (SNPs) genotyped in 1560 family members from 117 families densely affected by alcohol use disorders, recruited in the Collaborative Study on the Genetics of Alcoholism. Genome-wide significant association was found with several SNPs on chromosome 21 in KCNJ6 (a potassium inward rectifier channel; KIR3.2/GIRK2), with the most significant SNP at P = 4.7 × 10(-10)). The same SNPs were also associated with EROs from central and parietal electrodes, but with less significance, suggesting that the association is frontally focused. One imputed synonymous SNP in exon four, highly correlated with our top three SNPs, was significantly associated with the frontal theta ERO phenotype. These results suggest KCNJ6 or its product GIRK2 account for some of the variations in frontal theta band oscillations. GIRK2 receptor activation contributes to slow inhibitory postsynaptic potentials that modulate neuronal excitability, and therefore influence neuronal networks.
authors.affiliation: Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kang
authors.forename: M
authors.initials: M
authors.lastname: Rangaswamy
authors.forename: N
authors.initials: N
authors.lastname: Manz
authors.forename: J-C
authors.initials: JC
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Wetherill
authors.forename: T
authors.initials: T
authors.lastname: Hinrichs
authors.forename: L
authors.initials: L
authors.lastname: Almasy
authors.forename: A
authors.initials: A
authors.lastname: Brooks
authors.forename: D B
authors.initials: DB
authors.lastname: Chorlian
authors.forename: D
authors.initials: D
authors.lastname: Dick
authors.forename: V
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: J
authors.initials: J
authors.lastname: Kramer
authors.forename: S
authors.initials: S
authors.lastname: Kuperman
authors.forename: J
authors.initials: J
authors.lastname: Nurnberger
authors.forename: J
authors.initials: J
authors.lastname: Rice
authors.forename: M
authors.initials: M
authors.lastname: Schuckit
authors.forename: J
authors.initials: J
authors.lastname: Tischfield
authors.forename: L J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: A
authors.initials: A
authors.lastname: Goate
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.forename: B
authors.initials: B
authors.lastname: Porjesz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics; D002648:Child; D005192:Family Health; D005260:Female; D005625:Frontal Lobe / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013826:Theta Rhythm / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C094401:KCNJ6 protein, human