Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with ‘pleasurable buzz’ during early experimentation with smoking

Sherva, Richard; Wilhelmsen, Kirk; Pomerleau, Cynthia S.; Chasse, Scott A.; Rice, John P.; Snedecor, Sandy M.; Bierut, Laura J.; Neuman, Rosalind J.; Pomerleau, Ovide F.

doi:10.1111/j.1360-0443.2008.02279.x

Cited by 144Smoking Behavior and CessationGenetic Associations and EpidemiologyNicotinic Acetylcholine Receptors Study

Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with ‘pleasurable buzz’ during early experimentation with smoking

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Sherva, Richard, Wilhelmsen, Kirk, Pomerleau, Cynthia S., Chasse, Scott A., Rice, John P., Snedecor, Sandy M., Bierut, Laura J., Neuman, Rosalind J. +1 more·2008·Addiction

DOI 10.1111/j.1360-0443.2008.02279.xPMC PMC2582398

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Abstract

Aims To extend the previously identified association between a single nucleotide polymorphism (SNP) in neuronal acetylcholine receptor subunit alpha‐5 (CHRNA5) and nicotine dependence to current smoking and initial smoking‐experience phenotypes. Design, setting, participants Case–control association study with a community‐based sample, comprising 363 Caucasians and 72 African Americans (203 cases, 232 controls). Measurements Cases had smoked ≥ five cigarettes/day for ≥ 5 years and had smoked at their current rate for the past 6 months. Controls had smoked between one and 100 cigarettes in their life‐time, but never regularly. Participants also rated, retrospectively, pleasurable and displeasurable sensations experienced when they first smoked. We tested for associations between smoking phenotypes and the top 25 SNPs tested for association with nicotine dependence in a previous study. Findings A non‐synonymous coding SNP in CHRNA5, rs16969968, was associated with case status [odds ratio (OR) = 1.5,P = 0.01] and, in Caucasians, with experiencing a pleasurable rush or buzz during the first cigarette (OR = 1.6,P = 0.01); these sensations were associated highly with current smoking (OR = 8.2,P = 0.0001). Conclusions We replicated the observation that the minor allele of rs16969968 affects smoking behavior, and extended these findings to sensitivity to smoking effects upon experimentation. While the ability to test genetic associations was limited by sample size, the polymorphism in the CHRNA5 subunit was shown to be associated significantly with enhanced pleasurable responses to initial cigarettes in regular smokers in an a priori test. The findings suggest that phenotypes related to subjective experiences upon smoking experimentation may mediate the development of nicotine dependence.

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The association with rs16969968 has been replicated either directly or using highly correlated SNPs by several groups.
“This association has been replicated either directly or using highly correlated SNPs by several groups (92–97).”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [94]

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buzz ’ during early experimentation with
Sherva, R., Wilhelmsen, K. C., Pomerleau, C. S., Chasse, S. A., Rice, J. P., Snedecor, Y. M., Bierut, L. J., Neuman, R. J., & Pomerleau, O. F. (2016)
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CHRNA5 Polymorphism (Rs16969968) and Its Association with Nicotine Dependence among Smokers 105
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Exploration of the role of CHRNA5-A3-B4 genotype in smoking behavioursPreprint
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From Men to Mice: CHRNA5/CHRNA3, Smoking Behavior and Disease
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Authors: Sherva, R., Wilhelmsen, K., Pomerleau, C. S., Chasse, S. A., Rice, J. P., Snedecor, S. M., Bierut, L. J., Neuman, R. J., & Pomerleau, O. F.
Affiliations: Washington University in St. Louis (US)
University of North Carolina at Chapel Hill (US)
University of Michigan (US)
Corresponding author: Pomerleau, Ovide F.
ORCID: Sherva, Richard
Wilhelmsen, Kirk
Rice, John P.
Bierut, Laura J.
Pomerleau, Ovide F.
Venue: Addiction
Publisher: Wiley
Published: 2008-08-07
Volume: 103
Issue: 9
Pages: 1544-1552
ISSN: 0965-2140 (ISSN-L)
1360-0443
DOI: 10.1111/j.1360-0443.2008.02279.x
PMC: PMC2582398
OpenAlex: W2132690415
Cited by: 143
References: 43
Citations by year: 2025: 2 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 3 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 3 · 2016: 4 · 2015: 11 · 2014: 4 · 2013: 9 · 2012: 17
FWCI: 11.74
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Addiction (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
Deep Blue (University of Michigan) (submittedVersion)
UNC Libraries
Funders: National Institutes of Health
National Institute of Mental Health (T32MH014677)
National Institute on Drug Abuse (R01DA006529, K02DA021237, R01DA017640)
National Cancer Institute (P01CA089392)
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: CHRNA5, rs16969968, single nucleotide polymorphisms, smoking status, nicotine dependence, smoking initiation, genetic susceptibility to smoking
MeSH terms: Smoking Prevention, Adult, Female, Humans, Male, Nerve Tissue Proteins, Receptors, Nicotinic, Sensation, Smoking, Tobacco Use Disorder, Case-Control Studies, Polymorphism, Single Nucleotide

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Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with ‘pleasurable buzz’ during early experimentation with smoking

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