Linkage disequilibrium, haplotype and association studies of a chromosome 4 GABA receptor gene cluster: candidate gene variants for addictions
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Strong genetic contributions to individual differences in vulnerability to addictions are well supported by classical genetic studies. Linkage and association genome scans for addiction vulnerability have provided converging evidence for several chromosomal regions which are likely to harbor allelic variants that contribute to such vulnerability. We and others have delineated a candidate addiction-associated chromosome 4p12 "rSA3" region based on convergent data from association genome scanning studies in polysubstance abusers [Uhl et al. (2001); Am J Hum Genet 69(6):1290-1300], linkage-based studies in alcoholism [Long et al. (1998); Am J Med Genet 81(3):216-221; Reich et al. (1998); Am J Med Genet 81(3):207-215] and association-based studies for alcoholism and association-based studies for individual differences in electroencephalographic (EEG) spectral power phenotypes [Porjesz et al. (2002); Proc Natl Acad Sci USA 99(6):3729-3733; Edenberg et al. (2004); Am J Hum Genet 74(4):705-714]. The rSA3 region contains interesting candidate genes that encode the alpha 2, alpha 4, beta 1, and gamma 1 receptor subunits for the principal brain inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) [Covault et al. (2004); Am J Med Genet Part B 129B:104-109; Edenberg et al. (2004); Am J Hum Genet 74(4):705-714; Lappalainen et al. (2005); Alcohol Clin Exp Res 29(4):493-498]. We now report assessment of single nucleotide polymorphism (SNP) genotypes in this region in three samples of substance abusers and controls. These results delineate the haplotypes and patterns of linkage disequilibrium in this region, focus attention of the GABRA2 gene and identify modest associations between GABRA2 genotypes and addiction phenotypes. These results are consistent with modest roles for GABRA2 variants in addiction vulnerabilities.
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GABAARs in brain reward circuits may be involved in the development of brain changes that mediate the addictive properties of drugs in general.
“The involvement of GABAAR genes in the abuse of and dependence on drugs that do not directly affect the GABAARs suggest that the GABAARs in brain reward circuits may be involved in the development of brain changes that mediate the addictive properties of drugs in general.”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [103]
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- Authors
- Drgon, T., D'Addario, C., & Uhl, G. R.
- Affiliations
- United States Department of Health and Human Services (US)
- Corresponding author
- Uhl, George R.
- ORCID
- Uhl, George R.
- Venue
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2006-11-22
- Volume
- 141B
- Issue
- 8
- Pages
- 854-860
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC3922197
- OpenAlex
- W2087346597
- Cited by
- 82
- References
- 38
- Citations by year
- 2022: 1 · 2021: 1 · 2020: 1 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 3 · 2012: 13
- FWCI
- 4.37
- 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)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse (Z01DA000401, K08DA000401)
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- linkage disequilibrium, haplotypes, GABRA2, GABAA receptor, addiction vulnerability, substance abuse, alcoholism, single nucleotide polymorphisms, genetic association, GABA receptor subunits, EEG spectral power, candidate genes, GABRA4, GABRB1, haplotype structure
- MeSH terms
- Black or African American, Chromosomes, Human, Pair 4, Genotype, Haplotypes, Humans, Maryland, Receptors, GABA-A, Linkage Disequilibrium, DNA Primers, Substance-Related Disorders, Genetic Predisposition to Disease, Gene Components, White People
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