ArticleAlcoholism, clinical and experimental research2015
GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures.
Article in Alcoholism, clinical and experimental research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020Pooled it
- GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose-Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers.Alcoholism, clinical and experimental research · 2017Trial
- Association Between GABRG2 and Self-Rating of the Effects of Alcohol in a French Young Adult Sample.Risk management and healthcare policy · 2025Article
- GABRG2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics.Journal of translational medicine · 2024Review
- 5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.Genes, brain, and behavior · 2023Review
- Prospective DNA Methylation Analysis of the CpG GABRA2 Receptor Subunit in Alcohol Dependence during Detoxification.Medicina (Kaunas, Lithuania) · 2022Article
- Sex differences in GABAGenes, brain, and behavior · 2022Article
- A quantitative trait variant in Gabra2 underlies increased methamphetamine stimulant sensitivity.Genes, brain, and behavior · 2021Article
- Article
- 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
- Molecular Correlates of Topiramate and GRIK1 rs2832407 Genotype in Pluripotent Stem Cell-Derived Neural Cultures.Alcoholism, clinical and experimental research · 2020Article
- Alcohol-responsive genes identified in human iPSC-derived neural cultures.Translational psychiatry · 2019Article
- Identification of a Functional Non-coding Variant in the GABAFrontiers in genetics · 2019Article
- Prevalence of Some Genetic Risk Factors for Nicotine Dependence in Ukraine.Genetics research international · 2019Article
- Early-life adversity selectively impairs α2-GABANeuropharmacology · 2018Article
- Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells?Alcoholism, clinical and experimental research · 2018Review
- GABRA2 rs279858-linked variants are associated with disrupted structural connectome of reward circuits in heroin abusers.Translational psychiatry · 2018Article
- GABAPsychopharmacology · 2018Review
- Examining the effects of alcohol on GABAAlcohol (Fayetteville, N.Y.) · 2018Article
- Uncovering True Cellular Phenotypes: Using Induced Pluripotent Stem Cell-Derived Neurons to Study Early Insults in Neurodevelopmental Disorders.Frontiers in neurology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGenetic variation in a region of chromosome 4p12 that includes the GABAA subunit gene GABRA2 has been reproducibly associated with alcohol dependence (AD). However, the molecular mechanisms underlying the association are unknown. This study examined correlates of in vitro gene expression of the AD-associated GABRA2 rs279858*C-allele in human neural cells using an induced pluripotent stem cell (iPSC) model system.
methodsWe examined mRNA expression of chromosome 4p12 GABAA subunit genes (GABRG1, GABRA2, GABRA4, and GABRB1) in 36 human neural cell lines differentiated from iPSCs using quantitative polymerase chain reaction and next-generation RNA sequencing. mRNA expression in adult human brain was examined using the BrainCloud and BRAINEAC data sets.
resultsWe found significantly lower levels of GABRA2 mRNA in neural cell cultures derived from rs279858*C-allele carriers. Levels of GABRA2 RNA were correlated with those of the other 3 chromosome 4p12 GABAA genes, but not other neural genes. Cluster analysis based on the relative RNA levels of the 4 chromosome 4p12 GABAA genes identified 2 distinct clusters of cell lines, a low-expression cluster associated with rs279858*C-allele carriers and a high-expression cluster enriched for the rs279858*T/T genotype. In contrast, there was no association of genotype with chromosome 4p12 GABAA gene expression in postmortem adult cortex in either the BrainCloud or BRAINEAC data sets.
conclusionsAD-associated variation in GABRA2 is associated with differential expression of the entire cluster of GABAA subunit genes on chromosome 4p12 in human iPSC-derived neural cell cultures. The absence of a parallel effect in postmortem human adult brain samples suggests that AD-associated genotype effects on GABAA expression, although not present in mature cortex, could have effects on regulation of the chromosome 4p12 GABAA cluster during neural development.
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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.