Family-based genome-wide association study of frontal theta oscillations identifies potassium channel gene KCNJ6

S. J. Kang, M. Rangaswamy, N. Manz, J. C. Wang, L. Wetherill, T. Hinrichs, L. Almasy, A. Brooks, D. B. Chorlian, D. Dick, V. Hesselbrock, J. Kramer, S. Kuperman, John Nurnberger, J. Rice, M. Schuckit, J. Tischfield, L. J. Bierut, Howard Edenberg, A. GoateTatiana Foroud, B. Porjesz

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)712-719
Number of pages8
JournalGenes, Brain and Behavior
Volume11
Issue number6
DOIs
StatePublished - Aug 2012

Fingerprint

Genome-Wide Association Study
Potassium Channels
Single Nucleotide Polymorphism
Alcoholism
Genes
Inwardly Rectifying Potassium Channel
Endophenotypes
Phenotype
Chromosomes, Human, Pair 21
Inhibitory Postsynaptic Potentials
Alcoholics
Exons
Electrodes
Alcohols
Genome

Keywords

  • Alcoholism
  • EEG
  • GWAS
  • KCNJ6
  • Oscillations

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

Kang, S. J., Rangaswamy, M., Manz, N., Wang, J. C., Wetherill, L., Hinrichs, T., ... Porjesz, B. (2012). Family-based genome-wide association study of frontal theta oscillations identifies potassium channel gene KCNJ6. Genes, Brain and Behavior, 11(6), 712-719. https://doi.org/10.1111/j.1601-183X.2012.00803.x

Family-based genome-wide association study of frontal theta oscillations identifies potassium channel gene KCNJ6. / Kang, S. J.; Rangaswamy, M.; Manz, N.; Wang, J. C.; Wetherill, L.; Hinrichs, T.; Almasy, L.; Brooks, A.; Chorlian, D. B.; Dick, D.; Hesselbrock, V.; Kramer, J.; Kuperman, S.; Nurnberger, John; Rice, J.; Schuckit, M.; Tischfield, J.; Bierut, L. J.; Edenberg, Howard; Goate, A.; Foroud, Tatiana; Porjesz, B.

In: Genes, Brain and Behavior, Vol. 11, No. 6, 08.2012, p. 712-719.

Research output: Contribution to journalArticle

Kang, SJ, Rangaswamy, M, Manz, N, Wang, JC, Wetherill, L, Hinrichs, T, Almasy, L, Brooks, A, Chorlian, DB, Dick, D, Hesselbrock, V, Kramer, J, Kuperman, S, Nurnberger, J, Rice, J, Schuckit, M, Tischfield, J, Bierut, LJ, Edenberg, H, Goate, A, Foroud, T & Porjesz, B 2012, 'Family-based genome-wide association study of frontal theta oscillations identifies potassium channel gene KCNJ6', Genes, Brain and Behavior, vol. 11, no. 6, pp. 712-719. https://doi.org/10.1111/j.1601-183X.2012.00803.x
Kang, S. J. ; Rangaswamy, M. ; Manz, N. ; Wang, J. C. ; Wetherill, L. ; Hinrichs, T. ; Almasy, L. ; Brooks, A. ; Chorlian, D. B. ; Dick, D. ; Hesselbrock, V. ; Kramer, J. ; Kuperman, S. ; Nurnberger, John ; Rice, J. ; Schuckit, M. ; Tischfield, J. ; Bierut, L. J. ; Edenberg, Howard ; Goate, A. ; Foroud, Tatiana ; Porjesz, B. / Family-based genome-wide association study of frontal theta oscillations identifies potassium channel gene KCNJ6. In: Genes, Brain and Behavior. 2012 ; Vol. 11, No. 6. pp. 712-719.
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