Publication Details

Molecular genetics of successful smoking cessation: convergent genome-wide association study results.

Authors:Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE, David SP, Niaura R, Lerman C
Title:Molecular genetics of successful smoking cessation: convergent genome-wide association study results.
Journal:Archives of general psychiatry Jun 2008 , Vol 65 , pp. 683-93
Abstract:Smoking remains a major public health problem. Twin studies indicate that the ability to quit smoking is substantially heritable, with genetics that overlap modestly with the genetics of vulnerability to dependence on addictive substances.To identify replicated genes that facilitate smokers\' abilities to achieve and sustain abstinence from smoking (herein after referred to as quit-success genes) found in more than 2 genome-wide association (GWA) studies of successful vs unsuccessful abstainers, and, secondarily, to nominate genes for selective involvement in smoking cessation success with bupropion hydrochloride vs nicotine replacement therapy (NRT).The GWA results in subjects from 3 centers, with secondary analyses of NRT vs bupropion responders.Outpatient smoking cessation trial participants from 3 centers.European American smokers who successfully vs unsuccessfully abstain from smoking with biochemical confirmation in a smoking cessation trial using NRT, bupropion, or placebo (N = 550).Quit-success genes, reproducibly identified by clustered nominally positive single-nucleotide polymorphisms (SNPs) in more than 2 independent samples with significant P values based on Monte Carlo simulation trials. The NRT-selective genes were nominated by clustered SNPs that display much larger t values for NRT vs placebo comparisons. The bupropion-selective genes were nominated by bupropion-selective results.Variants in quit-success genes are likely to alter cell adhesion, enzymatic, transcriptional, structural, and DNA, RNA, and/or protein-handling functions. Quit-success genes are identified by clustered nominally positive SNPs from more than 2 samples and are unlikely to represent chance observations (Monte Carlo P< .0003). These genes display modest overlap with genes identified in GWA studies of dependence on addictive substances and memory.These results support polygenic genetics for success in abstaining from smoking, overlap with genetics of substance dependence and memory, and nominate gene variants for selective influences on therapeutic responses to bupropion vs NRT. Molecular genetics should help match the types and/or intensity of antismoking treatments with the smokers most likely to benefit from them.   PUBMED: 18519826
Ontological Annotations:
  • D002448: Cell Adhesion (Publication, NCBO Annotator)
  • D006801: Humans (PubMed MeSH Annotations)
  • D008568: Memory (Publication, NCBO Annotator)
  • D016642: Bupropion (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D014029: Tobacco Use Disorder (PubMed MeSH Annotations)
  • D001076: Aptitude (Publication, NCBO Annotator)
  • D009010: Monte Carlo Method (PubMed MeSH Annotations)
  • D012907: Smoking (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D004247: DNA (Publication, NCBO Annotator)
  • D008967: Molecular Biology (Publication, NCBO Annotator)
  • D014427: Twins (Publication, NCBO Annotator)
  • D020641: Polymorphism, Single Nucleotide (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D004305: Dose-Response Relationship, Drug (PubMed MeSH Annotations)
  • D016678: Genome (PubMed MeSH Annotations)
  • D002477: Cells (Publication, NCBO Annotator)
  • D000328: Adult (PubMed MeSH Annotations)
  • D020022: Genetic Predisposition to Disease (PubMed MeSH Annotations)
  • D010045: Outpatients (Publication, NCBO Annotator)
  • D018486: Twin Study (Publication, NCBO Annotator)
  • D004311: Double-Blind Method (PubMed MeSH Annotations)
  • GO:0005623: cell (Publication, NCBO Annotator)
  • D055106: Genome-Wide Association Study (Publication, NCBO Annotator)
  • D011634: Public Health (Publication, NCBO Annotator)
  • D001244: Association (Publication, NCBO Annotator)
  • D000483: Alleles (PubMed MeSH Annotations)
  • D016896: Treatment Outcome (PubMed MeSH Annotations)
  • D002874: Chromosome Mapping (PubMed MeSH Annotations)
  • D019966: Substance-Related Disorders (Publication, NCBO Annotator)
  • D012313: RNA (Publication, NCBO Annotator)
  • D014644: Genetic Variation (PubMed MeSH Annotations)
  • D005823: Genetics (Publication, NCBO Annotator)
  • D018849: Controlled Clinical Trials as Topic (PubMed MeSH Annotations)
  • GO:0007613: memory (Publication, NCBO Annotator)
  • D018687: Antidepressive Agents, Second-Generation (PubMed MeSH Annotations)
  • D009538: Nicotine (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • GO:0007155: cell adhesion (Publication, NCBO Annotator)
  • D016540: Smoking Cessation (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D005819: Genetic Markers (PubMed MeSH Annotations)
  • D013812: Therapeutics (Publication, NCBO Annotator)
  • D018722: Nicotinic Agonists (PubMed MeSH Annotations)
  • D006262: Health (Publication, NCBO Annotator)

1 GeneSets from this Publication:

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Expand Tier III Human 92 Genes GS14904: Genes Harboring Allelic Variants That Distinguish Successful vs Unsuccessful Nicotine Abstainers in at Least 2 Samples