Systematic Analysis of Glutamatergic Neurotransmission Genes in Alcohol Dependence and Adolescent Risky Drinking Behavior

Schumann, Gunter; Johann, Monika; Frank, Josef; Preuss, Ulrich W.; Dahmen, Norbert; Laucht, Manfred; Rietschel, Marcella; Rujescu, Dan; Lourdusamy, Anbarasu; Clarke, Toni‐Kim; Krause, Kristina; Dyer, Anne; Depner, Martin; Wellek, Stefan; Treutlein, Jens; Szegedi, Armin; Giegling, Ina; Cichon, Sven; Blomeyer, Dorothea; Heinz, Andreas; Heath, Simon; Lathrop, Mark; Wodarz, Norbert; Soyka, Michael; Spanagel, Rainer; Mann, Karl

doi:10.1001/archpsyc.65.7.826

Cited by 111 publications

(85 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…self-report on the effects of ethanol, subjective high assessment, body sway [180]) showed a systematic distribution difference in 173 genes, including CDH13 and XRCC5 , which had been identified as susceptibility genes for ethanol sensitivity and alcohol dependence elsewhere [161,181,182]. Multiple genes identified in the GSEA were related to glutamatergic signaling, a finding well in line with previous results of animal studies and candidate gene analyses [183,184]. Additionally, the muscarinic receptor (CHRM2) has been replicated in 2 GWAS [185,186] and several other well-replicated candidate genes (i.e.…”

Section: From Genes To Pathwayssupporting

confidence: 61%

Genetics of Alcohol Dependence: A Review of Clinical Studies

Samochowiec

Puls

et al. 2014

Neuropsychobiology

View full text Add to dashboard Cite

Background/Aims: Alcohol dependence is a common severe psychiatric disorder with a multifactorial etiology. Since the completion of the human genome project and with the increased availability of high-throughput genotyping, multiple genetic risk factors for substance-related disorders, including alcohol dependence, have been identified, but not all results could be replicated. Methods: We systematically review the clinical literature on genetic risk factors for alcohol dependence and alcohol-related phenotypes, including candidate gene-based studies, linkage studies and genome-wide association studies (GWAS). Results: Irrespectively of the methodology employed, the most robust findings regarding genetic risk factors for alcohol dependence concern genetic variations that affect alcohol metabolism. GWAS confirm the importance of the alcohol dehydrogenase gene cluster on chromosome 4 in the genetic risk for alcohol dependence with multiple variants that exert a small, but cumulative influence. A single variant with strong influence on individual risk is the aldehyde dehydrogenase 2 ALDHD2*2 variant common in Asian populations. Other robust associations have been found with previously uncharacterized genes like KIAA0040, and such observations can lead to the identification of thus far unknown signaling pathways. Converging evidence also points to a role of glutamatergic, dopaminergic and serotonergic neurotransmitter signaling in the risk for alcohol dependence, but effects are small, and gene-environment interactions further increase the complexity. Conclusion: With few exceptions like ALDH2*2, the contribution of individual genetic variants to the risk for alcohol-related disorders is small. However, the concentration of risk variants within neurotransmitter signaling pathways may help to deepen our understanding of the underlying pathophysiology and thereby contribute to develop novel therapeutic strategies.

show abstract

Section: From Genes To Pathwayssupporting

confidence: 61%

Genetics of Alcohol Dependence: A Review of Clinical Studies

Samochowiec

Puls

et al. 2014

Neuropsychobiology

View full text Add to dashboard Cite

show abstract

“…Previous studies on animal models reported acute liver failure due to increased extracellular concentration of glutamate in the brain [6] which was also correlated with arterial ammonia concentration [9]. Blocking of NMDA receptors through its antagonist MK-801 resulted in delay in the death of rats with acute liver failure supporting the role of NMDA receptors in this disease [24].…”

Section: Discussionmentioning

confidence: 75%

“…A variable GTn repeat in the 5'-regulatory region of N-methyl-Daspartate GRIN2A subtype was identified and significantly associated with alcohol dependence [14,23]. A study also showed GRIN2A gene to be of the highest relevance in alcohol dependence among ten glutamate pathway genes studied [24]. Recently, a study found SNPs of NMDA receptors' effect on neural activity of the brain related to alcohol cues and craving [25].…”

Section: Discussionmentioning

confidence: 97%

“…Activation of NMDA receptors leads to excitotoxicity and neuronal injury, which is associated with several diseases including acute and chronic liver failure [13,24]. Previous studies on animal models reported acute liver failure due to increased extracellular concentration of glutamate in the brain [6] which was also correlated with arterial ammonia concentration [9].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

An Association Study on the Glutamate Pathway GRIN2A Gene Polymorphisms with Heroin Dependence

Gupta¹,

Grover²,

Ambekar³

et al. 2017

J Addict Res Ther

View full text Add to dashboard Cite

Background: Heroin dependence (HD) is a complex disorder characterized by disruption in particular circuits of the brain and influenced by environmental and genetic factors. Glutamate pathway plays a role in normal brain functions including learning, memory, and cognition. Disturbances in Glutamate pathways are implicated in many psychiatric disorders, including heroin dependence, and polymorphisms present in these pathway genes are reported to increase the risk of developing heroin dependence.

show abstract

“…Recent evidence supports genetic associations with alcoholism of the glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene [57] and MAOA genes [27]. In future work, the contributions of the GRIN2A and MAOA genes to personality traits in alcohol dependence should be further tested.…”

Section: Alcoholismmentioning

confidence: 97%

Molecular Genetics of Human Personality Traits for Psychiatric, Behavioral, and Substance-Related Disorders

Lin¹,

Chen²

2009

TOTRANSMJ

View full text Add to dashboard Cite

Abstract:The investigation of personality genetics had received much attention since the three seminal reports showing an association between genes and personality traits in the general population. Accumulating evidences suggested that personality traits have significant genetic components. Although currently available data are not enough for proof, more and more genetic variants associated with personality traits are being discovered. In this paper, we review related studies of gene polymorphisms and human personality traits for psychiatric, behavioral, and substance-related disorders. First, we briefly describe the commonly-used self-reported temperament measures that define personality dimensions. Then, we summarize the characteristics of the candidate genes for personality traits, and investigate gene variants which have been suggested to be linked with personality traits for individuals with psychiatric, behavioral, and substance-related disorders.

show abstract

Systematic Analysis of Glutamatergic Neurotransmission Genes in Alcohol Dependence and Adolescent Risky Drinking Behavior

Abstract: Genetic variations in NR2A have the greatest relevance for human alcohol dependence among the glutamatergic genes selected for their known alteration of alcohol effects in animal models.

Cited by 111 publications

References 59 publications

Genetics of Alcohol Dependence: A Review of Clinical Studies

Genetics of Alcohol Dependence: A Review of Clinical Studies

An Association Study on the Glutamate Pathway GRIN2A Gene Polymorphisms with Heroin Dependence

Molecular Genetics of Human Personality Traits for Psychiatric, Behavioral, and Substance-Related Disorders

Contact Info

Product

Resources

About