Linkage disequilibrium between the beta frequency of the human EEG and a GABA
            <sub>A</sub>
            receptor gene locus

Porjesz, Bernice; Almasy, Laura; Edenberg, Howard J.; Wang, Kongming; Chorlian, David B.; Foroud, Tatiana; Goate, Alison M.; Rice, John P.; O’Connor, Sean; Rohrbaugh, John; Kuperman, Samuel; Bauer, Lance O.; Crowe, Raymond R.; Schuckit, Marc A.; Hesselbrock, Victor; Conneally, P. Michael; Tischfield, Jay A.; Li, Ting Kai; Reich, Theodore; Begleiter, Henri

doi:10.1073/pnas.052716399

Cited by 291 publications

(224 citation statements)

References 46 publications

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“…An interesting issue that is highlighted by the genetic studies of theta and delta oscillations is that these measures have provided significant clues to associations with transmitter-related genes -GABA A receptor gene and resting EEG beta band ( Porjesz et al, 2002 ); CHRM2 and theta and delta band for oddball targets . Furthermore these identified genetic locations also have significant associations with the diagnoses of alcohol dependence Wang et al, 2004 ).…”

Section: Resultsmentioning

confidence: 99%

Delta and theta oscillations as risk markers in adolescent offspring of alcoholics

Rangaswamy

Jones

Porjesz

et al. 2007

International Journal of Psychophysiology

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117

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Background-Visual P300 is consistently lower in alcohol dependent individuals, their offspring and subjects at risk. Delta and theta event related oscillations (ERO) are the major contributors to the P300 signal. The total and evoked power in delta and theta bands in the 300 to 700 millisecond post-stimulus window (corresponding to the zone of P3 maxima) was compared between adolescent offspring of alcoholics (high-risk) and age-matched normal controls (low-risk), to assess the utility of the risk markers.Methods-EEG was recorded during the performance of visual oddball task. The S-Transform algorithm decomposed the EEG signals into different frequency bands and the group differences in total and evoked power in the oscillatory responses during the P300 time window (300 to 700 ms) were analyzed using a multivariate design. Similar analysis was performed on P300 peak amplitudes for the target.Results-The high-risk group showed significantly lower parietal post-stimulus evoked and total power in the delta band for targets. A decrease in total power was seen centrally and parietally in theta band. The P300 peak amplitude in the parietal electrodes was also significantly lower in the high-risk group.Conclusions-The decreased total theta power and total and evoked delta power for visual targets in high risk individuals may serve as an endophenotypic marker in the development of alcoholism and other disinhibitory disorders. The differences seen between the offspring of alcoholics and controls may have a cholinergic basis. The ERO measures appear to be more robust than the P300 amplitude in differentiating the groups.

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Section: Resultsmentioning

confidence: 99%

Delta and theta oscillations as risk markers in adolescent offspring of alcoholics

Rangaswamy

Jones

Porjesz

et al. 2007

International Journal of Psychophysiology

Self Cite

117

136

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“…In neither case did [1][2][3] 0.015 CAG TGA SNP [2][3][4] 0.010 AGG GAA SNP [3][4][5] 0.044 GGG AAA SNP [4][5][6] 0.005 GGA AAG SNP [5][6][7] 0.065 GAA AGA* SNP [6][7][8] 0.027 AAC -SNP [7][8][9] 0.062 ACA* -SNP [8][9][10] 0.09 CAT** -SNP [9][10][11] 0.08 --SNP [10][11][12] 0.28 --SNP [11][12][13] 0.37 --SNP [12][13][14] 0.60 --SNP [13][14][15] 0.031 TGC TGT SNP [14][15][16] 0.057 GCA GTA SNP [15][16][17] 0.074 CCT** TAA SNP [16][17][18] 0.30 --Individual overtransmitted haplotypes for alcohol dependence are indicated in bold when P < 0.05; *P = 0.06, and **P < 0.10.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15][16] The lack of a clear pattern of inheritance suggests that multiple genes contribute to the risk for alcoholism. Several genes have already been identified by the Collaborative Study on the Genetics of Alcoholism (COGA), including GABRA2, 17,18 GABRG3, 19 CHRM2, 20,21 and hTAS2R16. 22 Each of these genes has a modest effect on the risk for alcohol dependence and it appears likely that additional genes contribute to the genetic susceptibility for alcohol dependence.…”

Section: Introductionmentioning

confidence: 99%

Association of the κ-opioid system with alcohol dependence

et al. 2006

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Opioid receptors and their endogenous peptide ligands play important roles in the reward and reinforcement of drugs such as heroin, cocaine, and alcohol. The binding of dynorphins to the j-opioid receptor has been shown to produce aversive states, which may prevent the development of reinforcement. We genotyped SNPs throughout OPRK1, encoding the j-opioid receptor, and PDYN, which encodes its ligand prodynorphin, in a group of 1860 European American individuals from 219 multiplex alcohol dependent families. Family-based analyses demonstrated associations between alcohol dependence and multiple SNPs in the promoter and 3 0 end of PDYN, and in intron 2 of OPRK1. Haplotype analyses further supported the association of PDYN. Thus, variations in the genes encoding both the j-opioid receptor and its ligand, OPRK1 and PDYN, are associated with the risk for alcohol dependence; this makes biological sense as variations in either should affect signaling through the j-opioid system.

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“…Earlier genomewide scans in American Indians and Caucasians have provided evidence for linkage of alcohol dependence and relapse-associated β EEG to chromosome 4p at the location of the GABA A gene cluster (Ghosh et al, 2003;Long et al, 1998;Porjesz et al, 2002;Reich et al, 1998;Zinn-Justin and Abel, 1999). Subsequently, several studies, nearly all in Caucasians, have found haplotype and SNP associations between GABRA2 and alcoholism.…”

Section: Gaba a Receptor Chromosome 4 Gene Clustermentioning

confidence: 99%

The role of GABAA receptors in the development of alcoholism

Enoch

2008

Pharmacology Biochemistry and Behavior

197

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Alcoholism is a common, heritable, chronic relapsing disorder. GABA A receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol including tolerance, dependence and withdrawal. Medications targeting GABA A receptors ameliorate the symptoms of acute withdrawal. Ethanol induces plasticity in GABA A receptors: tolerance is associated with generally decreased GABA A receptor activation and differentially altered subunit expression. The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction. VTA GABAergic interneurons are the primary inhibitory regulators of DA neurons and a subset of VTA GABA A receptors may be implicated in the switch from heavy drinking to dependence. GABA A receptors modulate anxiety and response to stress; important elements of sustained drinking and relapse. The GABA A receptor subunit genes clustered on chromosome 4 are highly expressed in the reward pathway. Several recent studies have provided strong evidence that one of these genes, GABRA2, is implicated in alcoholism in humans. The influence of the interaction between ethanol and GABA A receptors in the reward pathway on the development of alcoholism together with genetic and epigenetic vulnerabilities will be explored in this review.

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Linkage disequilibrium between the beta frequency of the human EEG and a GABA _A receptor gene locus

Cited by 291 publications

References 46 publications

Delta and theta oscillations as risk markers in adolescent offspring of alcoholics

Delta and theta oscillations as risk markers in adolescent offspring of alcoholics

Association of the κ-opioid system with alcohol dependence

The role of GABAA receptors in the development of alcoholism

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Linkage disequilibrium between the beta frequency of the human EEG and a GABA A receptor gene locus

Cited by 291 publications

References 46 publications

Delta and theta oscillations as risk markers in adolescent offspring of alcoholics

Delta and theta oscillations as risk markers in adolescent offspring of alcoholics

Association of the κ-opioid system with alcohol dependence

The role of GABAA receptors in the development of alcoholism

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Product

Resources

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Linkage disequilibrium between the beta frequency of the human EEG and a GABA _A receptor gene locus