GABRR1 and GABRR2, encoding the GABA‐A receptor subunits ρ1 and ρ2, are associated with alcohol dependence
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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).
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Human genetics studies have noted associations between GABAAR genes and different aspects of alcoholism.
“Human genetics studies have noted associations between GABAAR genes and different aspects of alcoholism [93-98].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [95]
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- Authors
- Xuei, X., Flury‐Wetherill, L., Dick, D., Goate, A., Tischfield, J., Nurnberger, J., Schuckit, M., Kramer, J., Kuperman, S., Hesselbrock, V., Porjesz, B., Foroud, T., & Edenberg, H. J.
- Affiliations
- Indiana University School of Medicine (US)
- Virginia Commonwealth University (US)
- Washington University in St. Louis (US)
- Rutgers, The State University of New Jersey (US)
- University of California San Diego (US)
- University of Iowa (US)
- UConn Health (US)
- Corresponding author
- Xuei, Xiaoling
- ORCID
- Venue
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2010-02-18
- Volume
- 153B
- Issue
- 2
- Pages
- 418-427
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC2829340
- OpenAlex
- W2017788834
- Cited by
- 47
- References
- 65
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 4
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by-nc-nd)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (NIAAA) (U10AA008401)
- National Institute on Drug Abuse (NIDA)
- Indiana Genomics Initiative of Indiana University (INGEN®)
- The Lilly Endowment, Inc.
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- GABAA receptor subunits, alcoholism, single nucleotide polymorphisms, family-based association, age of onset, GABA signaling, European Americans, multiplex families
- MeSH terms
- Alcoholism, Chromosome Mapping, Genotype, Haplotypes, Humans, Models, Genetic, Mutation, Phenotype, Receptors, GABA-A, Linkage Disequilibrium, Age of Onset, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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