Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence

Andrew C H Chen, Yongqiang Tang, Madhavi Rangaswamy, Jen C. Wang, Laura Almasy, Tatiana Foroud, Howard J. Edenberg, Victor Hesselbrock, John Nurnberger, Samuel Kuperman, Sean J. O'Connor, Marc A. Schuckit, Lance O. Bauer, Jay Tischfield, John P. Rice, Laura Bierut, Alison Goate, Bernice Porjesz

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Evidence suggests the P3 amplitude of the event-related potential and its underlying superimposed event-related oscillations (EROs), primarily in the theta (4-5 Hz) and delta (1-3 Hz) frequencies, as endophenotypes for the risk of alcoholism and other disinhibitory disorders. Major neurochemical substrates contributing to theta and delta rhythms and P3 involve strong GABAergic, cholinergic and glutamatergic system interactions. The aim of this study was to test the potential associations between single nucleotide polymorphisms (SNPs) in glutamate receptor genes and ERO quantitative traits. GRM8 was selected because it maps at chromosome 7q31.3-q32.1 under the peak region where we previously identified significant linkage (peak LOD=3.5) using a genome-wide linkage scan of the same phenotype (event-related theta band for the target visual stimuli). Neural activities recorded from scalp electrodes during a visual oddball task in which rare target elicited P3s were analyzed in a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) sample comprising 1,049 Caucasian subjects from 209 families (with 472 DSM-IV alcohol dependent individuals). The family-based association test (FBAT) detected significant association (P < 0.05) with multiple SNPs in the GRM8 gene and event-related theta power to target visual stimuli, and also with alcohol dependence, even after correction for multiple comparisons by false discovery rate (FDR). Our results suggest that variation in GRM8 may be involved in modulating event-related theta oscillations during information processing and also in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endo-phenotype approach in the genetic study of psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)359-368
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150
Issue number3
DOIs
StatePublished - Apr 5 2009
Externally publishedYes

Fingerprint

Glutamate Receptors
Alcoholism
Single Nucleotide Polymorphism
Genes
Delta Rhythm
Theta Rhythm
P300 Event-Related Potentials
Endophenotypes
Phenotype
Electrophysiology
Scalp
Automatic Data Processing
Diagnostic and Statistical Manual of Mental Disorders
Cholinergic Agents
Psychiatry
Electrodes
Chromosomes
Alcohols
Genome
Power (Psychology)

Keywords

  • Alcohol dependence
  • Disinhibition
  • Endopheno-type
  • Mglur8
  • P3

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence. / Chen, Andrew C H; Tang, Yongqiang; Rangaswamy, Madhavi; Wang, Jen C.; Almasy, Laura; Foroud, Tatiana; Edenberg, Howard J.; Hesselbrock, Victor; Nurnberger, John; Kuperman, Samuel; O'Connor, Sean J.; Schuckit, Marc A.; Bauer, Lance O.; Tischfield, Jay; Rice, John P.; Bierut, Laura; Goate, Alison; Porjesz, Bernice.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 150, No. 3, 05.04.2009, p. 359-368.

Research output: Contribution to journalArticle

Chen, ACH, Tang, Y, Rangaswamy, M, Wang, JC, Almasy, L, Foroud, T, Edenberg, HJ, Hesselbrock, V, Nurnberger, J, Kuperman, S, O'Connor, SJ, Schuckit, MA, Bauer, LO, Tischfield, J, Rice, JP, Bierut, L, Goate, A & Porjesz, B 2009, 'Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 150, no. 3, pp. 359-368. https://doi.org/10.1002/ajmg.b.30818
Chen, Andrew C H ; Tang, Yongqiang ; Rangaswamy, Madhavi ; Wang, Jen C. ; Almasy, Laura ; Foroud, Tatiana ; Edenberg, Howard J. ; Hesselbrock, Victor ; Nurnberger, John ; Kuperman, Samuel ; O'Connor, Sean J. ; Schuckit, Marc A. ; Bauer, Lance O. ; Tischfield, Jay ; Rice, John P. ; Bierut, Laura ; Goate, Alison ; Porjesz, Bernice. / Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2009 ; Vol. 150, No. 3. pp. 359-368.
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