GABAA receptor polymorphisms in alcohol use disorder in the GWAS era

  title={GABAA receptor polymorphisms in alcohol use disorder in the GWAS era},
  author={Mairi Koulentaki and Elias Kouroumalis},
Alcohol use disorder (AUD) is a chronic, relapsing, neuro-psychiatric illness of high prevalence and with a serious public health impact worldwide. It is complex and polygenic, with a heritability of about 50%, and influenced by environmental causal heterogeneity. Risk factors associated with its etiology have a genetic component. GABA (γ-aminobutyric acid) is a major inhibitory neurotransmitter in mammalian brain. GABAA receptors are believed to mediate some of the physiological and behavioral… Expand
Substance Dependence: Overview of the Environmental, Genetic, Epigenetic, and Imaging Studies
Brain imaging techniques like positron emission tomography/single-photon emission computed tomography can be helpful in the identification of neuroadaptive and neurodegenerative changes which in the future may help in the development of pharmacological treatment targets for SD. Expand
Novel molecular targets for treating alcohol use disorder and hepatotoxicity
The value of incorporating regulatory information and drug-protein interaction data to highlight promising molecular targets and drugs for treating AUD and ALD is demonstrated. Expand
Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects in Vivo
Novel information is provided supporting a role of missense GABA-A receptor polymorphisms in reaction time, motor time and effects of low ethanol doses in vivo. Expand
Leveraging genetic data to investigate molecular targets and drug repurposing candidates for treating alcohol use disorder and hepatotoxicity
This study demonstrates the value of incorporating regulatory information and drug-protein interaction data to highlight additional molecular targets and drug repurposing candidates for treating AUD and ALD. Expand
Alcohol-Related Central Nervous System Disorders Associated with Vitamin B Deficiency
Rare but severe central nervous system complications associated with vitamin B deficiency, such as Wernicke encephalopathy, Korsakoff syndrome, and Marchiafava–Bignami disease, have been reported asExpand
Female-specific decreases in alcohol binge-like drinking resulting from GABAA receptor delta-subunit knockdown in the VTA
Findings suggest sex differences and GABAAR subunit specificity in alcohol intake in male and female binge-like drinking in a critical area of mesolimbic circuitry—the ventral tegmental area (VTA). Expand


GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol dependence.
The role of GABRA2 haplotypes in the liability to alcohol dependence is confirmed and the three previous studies implicating a GABA-A receptor subunit as contributing to the genetic risk for alcohol dependence are extended. Expand
Allelic and haplotypic association of GABRA2 with alcohol dependence
Ten single nucleotide polymorphisms spanning the coding region of this gene were examined in samples of European American subjects with alcohol dependence, and controls screened to exclude substance use disorders, which underscore the potential contribution of polymorphic variation at the GABRA2 locus to the risk for alcohol dependence. Expand
Association of Gamma-Aminobutyric Acid A Receptor α2 Gene (GABRA2) with Alcohol Use Disorder
Findings from this extensive meta-analysis of five GABAA receptor genes and substance abuse support their involvement (with the best evidence for GABRA2) in the pathogenesis of AD. Expand
GABRA2 and alcohol use disorders: no evidence of an association in an Italian case-control study.
10 single nucleotide polymorphisms of the 3'-GABRA2 gene, previously reported to be implicated in alcohol dependence, were used to evaluate the linkage between selected SNPs and AUDs in an Italian sample and to compare findings with those of previous studies. Expand
Overview of the Genetics of Alcohol Use Disorder.
The most promising results associated with AUD and alcohol-related phenotypes have included SNPs of the alcohol metabolism genes ADH and ALDH, which have been found to be protective against the development of AUD. Expand
Association of GABRG3 with alcohol dependence.
The theory that the predisposition to alcoholism may be inherited as a general state of central nervous system disinhibition/hyperexcitability that results from an altered responsiveness to GABA is supported. Expand
Gamma-aminobutyric acid system genes--no evidence for a role in alcohol use and abuse in a community-based sample.
The results suggest that the relationship between alcohol use and GABA system genes may be limited to particular contexts, such as when accompanied by polysubstance abuse or a familial history of alcoholism. Expand
Association of GABAA receptors and alcohol dependence and the effects of genetic imprinting
  • Jiuzhou Z. Song, Daniel L. Koller, +9 authors H. Edenberg
  • Biology, Medicine
  • American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2003
Consistent, although weak, linkage disequilibrium between GABRB1 (located on chromosome 4) and alcoholism is found and these data are consistent with an association between the expressed alleles in the GABAA‐gene cluster on chromosome 15 and alcoholism that is modulated by genetic imprinting. Expand
Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations.
The very strong association of GABRA2 with both alcohol dependence and the beta frequency of the electroencephalogram, combined with biological evidence for a role of this gene in both phenotypes, suggest that GABra2 might influence susceptibility to alcohol dependence by modulating the level of neural excitation. Expand
Association of GABAA receptor α2 subunit gene (GABRA2) with alcohol dependence-related aggressive behavior
Findings support the involvement of GABRA2 gene in alcohol dependence-related aggressive behavior in subjects of Eastern European (Croatian) origin. Expand