SynthesisNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Association of gamma-aminobutyric acid A receptor α2 gene (GABRA2) with alcohol use disorder.
Synthesis in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 4 syntheses or guidelines pooled it, 97 citations in OpenAlex.
- Pooled it
- No association ofFrontiers in neurology · 2022Pooled it
- Genetics of methamphetamine use disorder: A systematic review and meta-analyses of gene association studies.Neuroscience and biobehavioral reviews · 2021Pooled it
- Genome-wide meta-analysis of copy number variations with alcohol dependence.The pharmacogenomics journal · 2018Pooled it
- Exploratory Analysis of Genetic Variants in BDNF, GABA Receptors, and Dopaminergic Pathways with Alcohol Use Disorder in a Spanish Cohort.International journal of molecular sciences · 2026Article
- Investigating metabotropic glutamate receptors as molecular targets for next-generation pharmacotherapies for alcohol use disorder.Expert opinion on therapeutic targets · 2026Review
- Genetic and Epigenetic Approaches to Opioid Use Disorder.Expert reviews in molecular medicine · 2025Review
- Common Genomic and Proteomic Alterations Related to Disturbed Neural Oscillatory Activity in Schizophrenia.International journal of molecular sciences · 2025Review
- Sex-Specific Concordance of Striatal Transcriptional Signatures of Opioid Addiction in Human and Rodent Brains.Biological psychiatry global open science · 2025Article
- Association Between GABRG2 and Self-Rating of the Effects of Alcohol in a French Young Adult Sample.Risk management and healthcare policy · 2025Article
- Transcriptome changes in the nucleus of the solitary tract induced by repeated stress, alcohol dependence, or stress-induced drinking in dependent mice.Neuropharmacology · 2024Article
- Understanding the Mechanisms of Action and Effects of Drugs of Abuse.Molecules (Basel, Switzerland) · 2023Review
- Sex differences in GABAGenes, brain, and behavior · 2022Article
- FACTORS CONTRIBUTING TO THE ESCALATION OF ALCOHOL CONSUMPTION.Neuroscience and biobehavioral reviews · 2022Review
- Genetic interactions with stressful environments in depression and addiction.BJPsych advances · 2021Article
- Confirmation of a CausalFrontiers in psychiatry · 2021Article
- Induced pluripotent stem cell reprogramming-associated methylation at the GABRA2 promoter and chr4p12 GABAAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2020Article
- Recent advances in genetic studies of alcohol use disorders.Current genetic medicine reports · 2020Article
- Developing neuroscience-based treatments for alcohol addiction: A matter of choice?Translational psychiatry · 2019Review
- Determining population stratification and subgroup effects in association studies of rare genetic variants for nicotine dependence.Psychiatric genetics · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in mammalian brain. GABA receptor are involved in a number of complex disorders, including substance abuse. No variants of the commonly studied GABA receptor genes that have been associated with substance dependence have been determined to be functional or pathogenic. To reconcile the conflicting associations with substance dependence traits, we performed a meta-analysis of variants in the GABAA receptor genes (GABRB2, GABRA6, GABRA1, and GABRG2 on chromosome 5q and GABRA2 on chromosome 4p12) using genotype data from 4739 cases of alcohol, opioid, or methamphetamine dependence and 4924 controls. Then, we combined the data from candidate gene association studies in the literature with two alcohol dependence (AD) samples, including 1691 cases and 1712 controls from the Study of Addiction: Genetics and Environment (SAGE), and 2644 cases and 494 controls from our own study. Using a Bonferroni-corrected threshold of 0.007, we found strong associations between GABRA2 and AD (P=9 × 10(-6) and odds ratio (OR) 95% confidence interval (CI)=1.27 (1.15, 1.4) for rs567926, P=4 × 10(-5) and OR=1.21 (1.1, 1.32) for rs279858), and between GABRG2 and both dependence on alcohol and dependence on heroin (P=0.0005 and OR=1.22 (1.09, 1.37) for rs211014). Significant association was also observed between GABRA6 rs3219151 and AD. The GABRA2 rs279858 association was observed in the SAGE data sets with a combined P of 9 × 10(-6) (OR=1.17 (1.09, 1.26)). When all of these data sets, including our samples, were meta-analyzed, associations of both GABRA2 single-nucleotide polymorphisms remained (for rs567926, P=7 × 10(-5) (OR=1.18 (1.09, 1.29)) in all the studies, and P=8 × 10(-6) (OR=1.25 (1.13, 1.38)) in subjects of European ancestry and for rs279858, P=5 × 10(-6) (OR=1.18 (1.1, 1.26)) in subjects of European ancestry. 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. Further replications with larger samples are warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.