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Cited by 186Smoking Behavior and CessationGenetic Associations and EpidemiologyNicotinic Acetylcholine Receptors Study

The CHRNA5/A3/B4 Gene Cluster Variability as an Important Determinant of Early Alcohol and Tobacco Initiation in Young Adults

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Schlaepfer, Isabel R., Hoft, Nicole R., Collins, Allan C., Corley, Robin P., Hewitt, John K., Hopfer, Christian J., Lessem, Jeffrey M., McQueen, Matthew B. +2 more·2008·Biological Psychiatry
DOI 10.1016/j.biopsych.2007.10.024PMC PMC2526976
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Abstract

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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  • Increased risk of tobacco dependence is associated with rs6495308, rs578776, or rs1051730 in CHRNA3, and with rs1948 in CHRNB4.

    “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

    The Results and Discussion report that the CC genotype of rs1948 in CHRNB4 predicts earlier tobacco initiation, including in a replication sample. They do not establish increased risk of tobacco dependence for rs1948. The other SNPs in the citing sentence are attributed to different sources, not to Schlaepfer et al. (LLM, conf=0.88)

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  1. [13]Madden PA, Heath AC, Martin NG. Smoking and intoxication after alcohol challenge in women and men: genetic influences. Alcohol Clin Exp Res. 1997;21:1732–41. [PubMed] [Google Scholar]

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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)
DOI
10.1016/j.biopsych.2007.10.024
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
Licence
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 › Physiology › 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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