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The CHRNA5/A3/B4 Gene Cluster Variability as an Important Determinant of Early Alcohol and Tobacco Initiation in Young Adults
Open accessAbstract
Background One potential site of convergence of the nicotine and alcohol actions is the family of the neuronal nicotinic acetylcholine receptors. Our study examines the genetic association between variations in the genomic region containing the CHRNA5, A3, and B4 gene cluster (A5A3B4) and several phenotypes of alcohol and tobacco use in an ethnically diverse young adult sample. Significant results were then replicated in a separate adult population-representative sample. Methods In a selected sample, nine single nucleotide polymorphisms (SNPs) were tested for association with various nicotine and alcohol phenotypes, including age of initiation and measures of frequency, quantity, and subjective responses to the substances. Analysis was conducted with the statistical genetics program WHAP in the full sample (1075 subjects) including ethnicities as covariates and within each ethnic group sub-sample. Replication of the significant results in a separate population-based sample was carried out with the PBAT statistical genetics program. Results Two linked SNPs (rs8023462 and rs1948) located in a conserved region of the A5A3B4 gene cluster significantly predicted early age of initiation for tobacco with a hazard ratio (HR) of 1.35 (95% confidence interval [CI]1.08-1.70) for the CC genotype of rs8023462 and a HR of 1.29 (95% CI 1.01-1.63) for the TT genotype of rs1948 [corrected]. These findings were then replicated in a separate population-representative sample, showing rs1948 and rs8023462 to be associated with age of initiation for both tobacco and alcohol use (p < .01 and p < .001). Conclusions Variations in A5A3B4 genes might influence behaviors that promote early age of experimentation with drugs.
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“In addition to the rs16969968 SNP in CHRNA5, there is also increased risk of tobacco dependence in individuals carrying the rs6495308, rs578776, or rs1051730 SNPs in CHRNA3 (Berrettini et al. 2008;Saccone et al. 2009), and rs1948 in CHRNB4 (Schlaepfer et al. 2008).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Schlaepfer et al. 2008
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Metadata
- Authors
- Schlaepfer, I. R., Hoft, N. R., Collins, A. C., Corley, R. P., Hewitt, J. K., Hopfer, C. J., Lessem, J. M., McQueen, M. B., Rhee, S. H., & Ehringer, M. A.
- Affiliations
- University of Colorado Boulder (US)
- University of Colorado Anschutz (US)
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 63
- Issue
- 11
- Pages
- 1039-1046
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2526976
- OpenAlex
- W2094802004
- Cited by
- 186
- References
- 53
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 8 · 2017: 13 · 2016: 10 · 2015: 13 · 2014: 8 · 2013: 17 · 2012: 21
- FWCI
- 15.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (EY012562, DA13956, DA011015, DA017637, DA03194, MH15442, HD010333, AA007464, MH001865, DA012845, AA11949-03)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- neuronal nicotinic acetylcholine receptors, age of alcohol initiation, single nucleotide polymorphisms, genetic association, young adults, nicotine use, alcohol consumption, substance use initiation, replication
- MeSH terms
- Adolescent, Adult, Alcoholism, Ethnicity, Female, Gene Frequency, Multigene Family, Genotype, Humans, Male, Nerve Tissue Proteins, Receptors, Nicotinic, Tobacco Use Disorder, Proportional Hazards Models, Age of Onset, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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