Loading...
Family-based genome-wide association study of frontal θ 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
Kang, S J
Rangaswamy, M
Manz, N
Wang, J-C
Wetherill, L
Hinrichs, T
Almasy, L
Brooks, A
Chorlian, D B
Dick, D
Citations
Altmetric:
Journal Title
Genes, brain, and behavior
Keywords
Readers/Advisors
Journal Title
Term and Year
Publication Date
2012-05-31
Type
Book Title
Publication Volume
11
Publication Issue
6
Publication Begin
712
Publication End
9
Number of pages
Collections
Files
Loading...
Article
Adobe PDF, 654.44 KB
Loading...
Supplementary material
Adobe PDF, 141.06 KB
Research Projects
Organizational Units
Journal Issue
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.
Citation
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 Jr, Rice J, Schuckit M, Tischfield J, Bierut LJ, Edenberg HJ, Goate A, Foroud T, Porjesz B. Family-based genome-wide association study of frontal θ oscillations identifies potassium channel gene KCNJ6. Genes Brain Behav. 2012 Aug;11(6):712-9. doi: 10.1111/j.1601-183X.2012.00803.x. Epub 2012 May 31. PMID: 22554406; PMCID: PMC3666338.