The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample.
- Authors
- Lind, Penelope A; Macgregor, Stuart; Agrawal, Arpana; Montgomery, Grant W; Heath, Andrew C; Martin, Nicholas G; Whitfield, John B
- Year
- 2008
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 18727688
- DOI
- 10.1111/j.1530-0277.2008.00768.x
- PMCID
- PMC2575093
BACKGROUND: Multiple studies have shown that genetic variation in the alpha-2 subunit of the gamma-aminobutyric acid type A (GABA(A)) receptor (GABRA2) is associated with risk for alcohol dependence. Recent reports have suggested that GABRA2 may exert its influence on dependence through factors such as sensitivity to alcohol's intoxicating effects and that GABRA2 may also contribute to a common underlying genetic vulnerability to both alcohol and drug dependence. The present study tested for association between GABRA2 and alcohol dependence, smoking, and illicit drug use within the Australian population. METHODS: We genotyped 11 single nucleotide polymorphisms (SNPs) within or flanking GABRA2 in 4597 subjects (34.6% males) from 2618 families comprising 814 monozygotic pairs, 1177 dizygotic pairs, and 627 twins whose co-twin did not participate. Family-based association tests were conducted for binary and quantitative measures of alcohol dependence, smoking, and cannabis and other illicit drug use. RESULTS: We observed evidence of association (p < 0.05) between multiple GABRA2 SNPs and quantitative measures of alcohol dependence, including symptom scores and principal component factor scores from the 9 criteria for DSM-IV alcohol dependence, in the opposite direction to that previously reported. In contrast, GABRA2 was not associated overall with dichotomous measure of alcohol dependence nor with smoking, cannabis, or illicit drug use. CONCLUSIONS: The GABRA2 allelic associations found in clinical case-control studies have detectable but minor effects on DSM-defined alcohol dependence in the general community. Systematic comparisons of allelic effects on alcohol dependence in clinical cases and in the general community are required.
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|---|---|---|---|---|
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| GABA<sub>A</sub> subunit single nucleotide polymorphisms show sex-specific association to alcohol consumption and mental distress in a Norwegian population-based sample. | Moe JS et al. | β | 2022 | β |
| Sex differences in GABA<sub>A</sub> receptor subunit transcript expression are mediated by genotype in subjects with alcohol-related cirrhosis of the liver. | Ashton MK et al. | β | 2022 | β |
| The genetic aetiology of cannabis use: from twin models to genome-wide association studies and beyond. | Verweij KJH et al. | β | 2022 | β |
| Developmental Change in Adolescent Delinquency: Modeling Time-Varying Effects of a Preventative Intervention and GABRA2 Halpotype Linked to Alcohol Use. | Schlomer GL et al. | β | 2019 | β |
| Identification of a functional non-coding variant in the GABA<sub>A</sub> receptor Ξ±2 subunit of the C57BL/6J mouse reference genome: Major implications for neuroscience research | Mulligan MK et al. | β | 2019 | β |
| Identification of a Functional Non-coding Variant in the GABA <sub><i>A</i></sub> Receptor Ξ±2 Subunit of the C57BL/6J Mouse Reference Genome: Major Implications for Neuroscience Research. | Mulligan MK et al. | β | 2019 | β |
| Romantic Partner Alcohol Misuse Interacts with <i>GABRA2</i> Genotype to Predict Frequency of Drunkenness in Young Adulthood. | Gajos JM et al. | β | 2019 | β |
| An Emerging Circuit Pharmacology of GABA<sub>A</sub> Receptors. | Engin E et al. | β | 2018 | β |
| GABA<sub>A</sub> receptor polymorphisms in alcohol use disorder in the GWAS era. | Koulentaki M et al. | β | 2018 | β |
| Neural and psychological characteristics of college students with alcoholic parents differ depending on current alcohol use. | Brown-Rice KA et al. | β | 2018 | β |
| Pharmacogenetics of Cannabinoids. | Hryhorowicz S et al. | β | 2018 | β |
| PROSPER Intervention Effects on Adolescents' Alcohol Misuse Vary by GABRA2 Genotype and Age. | Russell MA et al. | β | 2018 | β |
| Dimensionality and Genetic Correlates of Problem Behavior in Low-Income African American Adolescents. | Latendresse SJ et al. | β | 2017 | β |
| Stressful life events increase aggression and alcohol use in young carriers of the GABRA2 rs279826/rs279858 A-allele. | Kiive E et al. | β | 2017 | β |
| The genetic epidemiology of substance use disorder: A review. | Prom-Wormley EC et al. | β | 2017 | β |
| Candidate genes for alcohol dependence: A genetic association study from India. | Malhotra S et al. | β | 2016 | β |
| Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium. | Stringer S et al. | β | 2016 | β |
| Mechanisms in the relation between GABRA2 and adolescent externalizing problems. | Wang FL et al. | β | 2016 | β |
| Association of gamma-aminobutyric acid A receptor Ξ±2 gene (GABRA2) with alcohol use disorder. | Li D et al. | β | 2014 | β |
| Deletion of the GABAA Ξ±2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking. | Dixon CI et al. | β | 2014 | β |
| Examination of genetic variation in GABRA2 with conduct disorder and alcohol abuse and dependence in a longitudinal study. | Melroy WE et al. | β | 2014 | β |
| Gamma-aminobutyric acid system genes--no evidence for a role in alcohol use and abuse in a community-based sample. | Irons DE et al. | β | 2014 | β |
| Genetic influences on alcohol use across stages of development: GABRA2 and longitudinal trajectories of drunkenness from adolescence to young adulthood. | Dick DM et al. | β | 2014 | β |
| Genetic variation in GABRA2 moderates peer influence on externalizing behavior in adolescents. | Villafuerte S et al. | β | 2014 | β |
| The Genetics, Neurogenetics and Pharmacogenetics of Addiction. | Demers CH et al. | β | 2014 | β |
| Impulsiveness mediates the association between GABRA2 SNPs and lifetime alcohol problems. | Villafuerte S et al. | β | 2013 | β |
| Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration. | Dixon CI et al. | β | 2012 | β |
| Genetics of GABAergic signaling in nicotine and alcohol dependence. | Cui WY et al. | β | 2012 | β |
| Identifying genetic variation for alcohol dependence. | Agrawal A et al. | β | 2012 | β |
| Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism. | Villafuerte S et al. | β | 2012 | β |
| The genetics of addiction-a translational perspective. | Agrawal A et al. | β | 2012 | β |
| The genetics of alcohol dependence: advancing towards systems-based approaches. | Palmer RH et al. | β | 2012 | β |
| Ξ±2-containing GABA(A) receptors: a target for the development of novel treatment strategies for CNS disorders. | Engin E et al. | β | 2012 | β |
| A candidate gene association study of alcohol consumption in young women. | Agrawal A et al. | β | 2011 | β |
| Genetic association study of GABRA2 single nucleotide polymorphisms and electroencephalography in alcohol dependence. | Lydall GJ et al. | β | 2011 | β |
| A genome-wide association study of alcohol dependence. | Bierut LJ et al. | β | 2010 | β |
| Behavioral genetics in antisocial spectrum disorders and psychopathy: a review of the recent literature. | Gunter TD et al. | β | 2010 | β |
| GABRR1 and GABRR2, encoding the GABA-A receptor subunits rho1 and rho2, are associated with alcohol dependence. | Xuei X et al. | β | 2010 | β |
| Linkage analysis of alcohol dependence symptoms in the community. | Hansell NK et al. | β | 2010 | β |
| Pharmacogenetics of alcohol and alcohol dependence treatment. | Kranzler HR et al. | β | 2010 | β |
| Candidate genes for cannabis use disorders: findings, challenges and directions. | Agrawal A et al. | β | 2009 | β |
| Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity. | Wang LL et al. | β | 2009 | β |