These authors contributed equally to this work.
Family-based genome-wide association study of frontal theta oscillations identifies potassium channel gene KCNJ6
Article first published online: 31 MAY 2012
© 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society
Genes, Brain and Behavior
Volume 11, Issue 6, pages 712–719, August 2012
How to Cite
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, J., Rice, J., Schuckit, M., Tischfield, J., Bierut, L. J., Edenberg, H. J., Goate, A., Foroud, T. and Porjesz, B. (2012), Family-based genome-wide association study of frontal theta oscillations identifies potassium channel gene KCNJ6. Genes, Brain and Behavior, 11: 712–719. doi: 10.1111/j.1601-183X.2012.00803.x
- Issue published online: 23 JUL 2012
- Article first published online: 31 MAY 2012
- Accepted manuscript online: 3 MAY 2012 12:07PM EST
- Received 2 March 2012, revised 27 April 2012, accepted for publication 30 April 2012
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.