title: Genome-wide association for smoking cessation success in a trial of precessation nicotine replacement.
abstract: Abilities to successfully quit smoking display substantial evidence for heritability in classic and molecular genetic studies. Genome-wide association (GWA) studies have demonstrated single-nucleotide polymorphisms (SNPs) and haplotypes that distinguish successful quitters from individuals who were unable to quit smoking in clinical trial participants and in community samples. Many of the subjects in these clinical trial samples were aided by nicotine replacement therapy (NRT). We now report novel GWA results from participants in a clinical trial that sought dose/response relationships for "precessation" NRT. In this trial, 369 European-American smokers were randomized to 21 or 42 mg NRT, initiated 2 wks before target quit dates. Ten-week continuous smoking abstinence was assessed on the basis of self-reports and carbon monoxide levels. SNP genotyping used Affymetrix 6.0 arrays. GWA results for smoking cessation success provided no P value that reached "genome-wide" significance. Compared with chance, these results do identify (a) more clustering of nominally positive results within small genomic regions, (b) more overlap between these genomic regions and those identified in six prior successful smoking cessation GWA studies and (c) sets of genes that fall into gene ontology categories that appear to be biologically relevant. The 1,000 SNPs with the strongest associations form a plausible Bayesian network; no such network is formed by randomly selected sets of SNPs. The data provide independent support, based on individual genotyping, for many loci previously nominated on the basis of data from genotyping in pooled DNA samples. These results provide further support for the idea that aid for smoking cessation may be personalized on the basis of genetic predictors of outcome.
authors.affiliation: Molecular Neurobiology Branch, National Institutes of Health Intramural Research Program, National Institute on Drug Abuse (NIH-IRP, NIDA), Baltimore, Maryland, United States of America. guhl@intra.nida.nih.gov
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Tomas
authors.initials: T
authors.lastname: Drgon
authors.forename: Catherine
authors.initials: C
authors.lastname: Johnson
authors.forename: Marco F
authors.initials: MF
authors.lastname: Ramoni
authors.forename: Frederique M
authors.initials: FM
authors.lastname: Behm
authors.forename: Jed E
authors.initials: JE
authors.lastname: Rose
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D002248:Carbon Monoxide / Q000032:analysis; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D009538:Nicotine / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics* / Q000628:therapy*; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D009538:Nicotine; D002248:Carbon Monoxide
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