GABRR1 and GABRR2, encoding the GABA-A receptor subunits rho1 and rho2, are associated with alcohol dependence.
- Authors
- Xuei, Xiaoling; Flury-Wetherill, Leah; Dick, Danielle; Goate, Alison; Tischfield, Jay; Nurnberger, John; Schuckit, Marc; Kramer, John; Kuperman, Sam; Hesselbrock, Victor; Porjesz, Bernice; Foroud, Tatiana; Edenberg, Howard J
- Year
- 2010
- Journal
- American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
- PMID
- 19536785
- DOI
- 10.1002/ajmg.b.30995
- PMCID
- PMC2829340
The genes encoding several GABA-A receptor subunits, including GABRA2, have been associated with alcoholism, suggesting that variations in gaba signaling contribute to risk. Therefore, as part of a comprehensive evaluation of the GABA receptor genes, we evaluated the potential association of GABRR1 and GABRR2, which encode the rho1 and rho2 subunits of the pentameric GABA-A/GABA-C receptors. GABRR1 and GABRR2 lie in a head to tail orientation spanning 137 kb on chromosome 6q14-16. We genotyped 73 single nucleotide polymorphisms (SNPs), covering both genes and extending 31 kb upstream of GABRR2 and 95 kb downstream of GABRR1, in a sample of 1923 European Americans from 219 multiplex alcohol-dependent families. Family-based association analyses demonstrated that SNPs in both GABRR1 and GABRR2 were significantly associated with alcohol dependence. Among the associated SNPs was rs282129, a coding SNP (Met430Thr) in GABRR2. Secondary analysis using a median split for age of onset suggests that the association is strongest when the analysis is focused upon those with earlier onset of alcohol dependence. Haplotypes in each gene were significantly overtransmitted to family members who did not meet criteria for alcohol dependence (P < 0.04), and a haplotype in GABRR2 was significantly overtransmitted to family members who met a broader definition of alcoholism (P = 0.002) as well as DSM-IV dependence (P = 0.04).
No figures extracted from this document.
No entities extracted from this document yet.
No uploaded files.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Disruption of <i>chrna5</i> blunts aversion and adaptive transcriptomic responses to nicotine and alcohol. | Goel T et al. | — | 2026 | → |
| RNA Sequencing Identified Differentially Expressed Genes in the Mesocorticolimbic and Nigrostriatal Systems of Compulsive METH-Taking Rats. | Adjei N et al. | — | 2025 | → |
| The Vodka Trial: Clinical and Genetic Characteristics of Alcohol Responsiveness in Laryngeal Dystonia. | O'Flynn LC et al. | — | 2025 | → |
| Transcriptome changes in the nucleus of the solitary tract induced by repeated stress, alcohol dependence, or stress-induced drinking in dependent mice. | Grantham EK et al. | — | 2024 | → |
| Genome-wide DNA methylation analysis in schizophrenia with tardive dyskinesia: a preliminary study. | Zhang P et al. | — | 2023 | → |
| The collaborative study on the genetics of alcoholism: Genetics. | Johnson EC et al. | — | 2023 | → |
| Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans. | Parker CC et al. | — | 2020 | → |
| Analysis of Modulation of the <i>ρ</i>1 GABA<sub>A</sub> Receptor by Combinations of Inhibitory and Potentiating Neurosteroids Reveals Shared and Distinct Binding Sites. | Germann AL et al. | — | 2020 | → |
| Nutritional Contingency Reduces Alcohol Drinking by Altering Central Neurotransmitter Receptor Gene Expression in Rats. | Villavasso S et al. | — | 2019 | → |
| An Emerging Circuit Pharmacology of GABA<sub>A</sub> Receptors. | Engin E et al. | — | 2018 | → |
| Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with Reaction Time, Motor Time, and Ethanol Effects <i>in Vivo</i>. | García-Martín E et al. | — | 2018 | → |
| Genetic Polymorphism of GABRR2 Modulates Individuals' General Cognitive Ability in Healthy Chinese Han People. | Ma Z et al. | — | 2017 | → |
| Mutation of the inhibitory ethanol site in GABA<sub>A</sub> ρ1 receptors promotes tolerance to ethanol-induced motor incoordination. | Blednov YA et al. | — | 2017 | → |
| Alcohol-related genes show an enrichment of associations with a persistent externalizing factor. | Ashenhurst JR et al. | — | 2016 | → |
| Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel. | Heusser SA et al. | — | 2016 | → |
| Identification of an Inhibitory Alcohol Binding Site in GABAA ρ1 Receptors. | Borghese CM et al. | — | 2016 | → |
| Potentiation of Gamma Aminobutyric Acid Receptors (GABAAR) by Ethanol: How Are Inhibitory Receptors Affected? | Förstera B et al. | — | 2016 | → |
| Gene network analysis shows immune-signaling and ERK1/2 as novel genetic markers for multiple addiction phenotypes: alcohol, smoking and opioid addiction. | Reyes-Gibby CC et al. | — | 2015 | → |
| Alcohol dependence: molecular and behavioral evidence. | Trudell JR et al. | — | 2014 | → |
| GABAA receptors containing ρ1 subunits contribute to in vivo effects of ethanol in mice. | Blednov YA et al. | — | 2014 | → |
| Genetics of alcoholism. | Edenberg HJ et al. | — | 2014 | → |
| Proteomic approaches and identification of novel therapeutic targets for alcoholism. | Gorini G et al. | — | 2014 | → |
| Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics. | Howard RJ et al. | — | 2014 | → |
| Genetic and neurophysiological correlates of the age of onset of alcohol use disorders in adolescents and young adults. | Chorlian DB et al. | — | 2013 | → |
| mRNA and protein expression for novel GABAA receptors θ and ρ2 are altered in schizophrenia and mood disorders; relevance to FMRP-mGluR5 signaling pathway. | Fatemi SH et al. | — | 2013 | → |
| Alcohol Dependence and Genes Encoding α2 and γ1 GABAA Receptor Subunits: Insights from Humans and Mice. | Borghese CM et al. | — | 2012 | → |
| Current perspectives on the neurobiology of drug addiction: a focus on genetics and factors regulating gene expression. | Duncan JR | — | 2012 | → |
| Effects of vigabatrin, an irreversible GABA transaminase inhibitor, on ethanol reinforcement and ethanol discriminative stimuli in mice. | Griffin WC et al. | — | 2012 | → |
| Genome-wide association study identifies 5q21 and 9p24.1 (KDM4C) loci associated with alcohol withdrawal symptoms. | Wang KS et al. | — | 2012 | → |
| A polymorphism of the CREB binding protein (CREBBP) gene is a risk factor for addiction. | Kumar D et al. | — | 2011 | → |
| A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. | Wang KS et al. | — | 2010 | → |
| An Update on GABAρ Receptors. | Martínez-Delgado G et al. | — | 2010 | → |
| Brain electrophysiological endophenotypes for externalizing psychopathology: a multivariate approach. | Gilmore CS et al. | — | 2010 | → |
| Genome-wide association study of alcohol dependence implicates a region on chromosome 11. | Edenberg HJ et al. | — | 2010 | → |
| Pharmacogenetics of alcohol and alcohol dependence treatment. | Kranzler HR et al. | — | 2010 | → |
| Variation at the GABAA receptor gene, Rho 1 (GABRR1) associated with susceptibility to bipolar schizoaffective disorder. | Green EK et al. | — | 2010 | → |