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Genetic Variants and Early Cigarette Smoking and Nicotine Dependence Phenotypes in Adolescents

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O'Loughlin, Jennifer, Sylvestre, Marie-Pierre, Labbe, Aurélie, Low, Nancy C., Roy-Gagnon, Marie-Hélène, Dugas, Erika N., Karp, Igor, Engert, James C.·2014·PLoS ONE
DOI 10.1371/journal.pone.0115716PMC PMC4278712
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Abstract

BACKGROUND: While the heritability of cigarette smoking and nicotine dependence (ND) is well-documented, the contribution of specific genetic variants to specific phenotypes has not been closely examined. The objectives of this study were to test the associations between 321 tagging single-nucleotide polymorphisms (SNPs) that capture common genetic variation in 24 genes, and early smoking and ND phenotypes in novice adolescent smokers, and to assess if genetic predictors differ across these phenotypes. METHODS: In a prospective study of 1294 adolescents aged 12-13 years recruited from ten Montreal-area secondary schools, 544 participants who had smoked at least once during the 7-8 year follow-up provided DNA. 321 single-nucleotide polymorphisms (SNPs) in 24 candidate genes were tested for an association with number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three clusters of ND symptoms representing withdrawal symptoms, use of nicotine for self-medication, and a general ND/craving symptom indicator). RESULTS: The pattern of SNP-gene associations differed across phenotypes. Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1, SLC6A3 (also known as DAT1)) were associated with at least one phenotype with a p-value <0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for the association between rs557748 in OPRM1 and the ND/craving and self-medication phenotypes were both 0.076. CONCLUSIONS: Because the genetic predictors differ, specific cigarette smoking and ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen of the 16 top-ranked SNPs identified in this study were from loci involved in dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3). IMPACT: Dopaminergic pathways may be salient during early smoking and the development of ND.

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  • None of those 16 top-ranked SNPs were significant when controlled for multiple comparisons.

    “In a recent study, 15 out of the 16 top-ranked single nucleotide polymorphisms associated with teen smoking or nicotine dependence were also found to be involved in dopaminergic signaling pathways, although none were significant when controlled for multiple comparisons (O'Loughlin et al. 2014).”

    From <scp>N</scp> icotine and the adolescent brain (2015) · cites this paper as O'Loughlin et al. 2014

  • 15 out of the 16 top-ranked single nucleotide polymorphisms associated with teen smoking or nicotine dependence were also found to be involved in dopaminergic signaling pathways.

    “In a recent study, 15 out of the 16 top-ranked single nucleotide polymorphisms associated with teen smoking or nicotine dependence were also found to be involved in dopaminergic signaling pathways, although none were significant when controlled for multiple comparisons (O'Loughlin et al. 2014).”

    From <scp>N</scp> icotine and the adolescent brain (2015) · cites this paper as O'Loughlin et al. 2014

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Cited by

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Authors
O'Loughlin, J., Sylvestre, M.-P., Labbe, A., Low, N. C., Roy-Gagnon, M.-H., Dugas, E. N., Karp, I., & Engert, J. C.
Affiliations
  • Centre Hospitalier de l’Université de Montréal (CA)
  • McGill University (CA)
  • Western University (CA)
  • McGill University Health Centre (CA)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-12-29
Volume
9
Issue
12
Pages
e115716
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0115716
PMC
PMC4278712
OpenAlex
W2006758057
Cited by
21
References
5
Citations by year
2025: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2
FWCI
0.89
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Papyrus : Institutional Repository (Université de Montréal) (submittedVersion, cc-by)
Funders
  • McGill University
  • Genome Canada
  • Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
adolescent smoking, nicotine dependence, genetic susceptibility, single nucleotide polymorphisms, candidate genes, dopaminergic pathways, ANKK1, DRD2, catechol-O-methyltransferase, OPRM1, dopamine transporter, nicotine withdrawal, craving, Fagerström Tolerance Questionnaire, smoking initiation
MeSH terms
Adolescent, Child, Dopamine, Female, Humans, Male, Phenotype, Smoking, Tobacco Use Disorder, Cohort Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, Metabolic Networks and Pathways

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