title: Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence.
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 endophenotype approach in the genetic study of psychiatric disorders.
authors.affiliation: Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Andrew C H
authors.initials: AC
authors.lastname: Chen
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Tang
authors.forename: Madhavi
authors.initials: M
authors.lastname: Rangaswamy
authors.forename: Jen C
authors.initials: JC
authors.lastname: Wang
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: John
authors.initials: J
authors.lastname: Nurnberger
authors.forename: Samuel
authors.initials: S
authors.lastname: Kuperman
authors.forename: Sean J
authors.initials: SJ
authors.lastname: O'Connor
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schuckit
authors.forename: Lance O
authors.initials: LO
authors.lastname: Bauer
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Laura
authors.initials: L
authors.lastname: Bierut
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D002874:Chromosome Mapping; D003700:Delta Rhythm; D039721:Diagnostic and Statistical Manual of Mental Disorders; D018913:Event-Related Potentials, P300 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D009991:Oscillometry; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D017470:Receptors, Glutamate / Q000235:genetics*; D013826:Theta Rhythm; D044465:White People / Q000235:genetics
chemical_list: D017470:Receptors, Glutamate