title: Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances.
abstract: Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts. We report data that validate a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances. In a cessation study, v1.0 genotype scores predicted ability to quit with P=0.00056 and area under receiver-operating characteristic curve 0.66. About 43% vs 13% quit in the upper vs lower genotype score terciles. Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use. Higher v1.0 scores were associated with (a) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence (P=0.0004) and (b) lower probabilities of membership in a class that reported escalating use (P=0.001). These results indicate that: (a) we have identified genetic predictors of smoking cessation success, (b) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and (c) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts.
authors.affiliation: Molecular Neurobiology Branch, NIH-IRP, NIDA, Baltimore, MD, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Uhl
authors.affiliation: Molecular Neurobiology Branch, NIH-IRP, NIDA, Baltimore, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Walther
authors.affiliation: Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Musci
authors.affiliation: Molecular Neurobiology Branch, NIH-IRP, NIDA, Baltimore, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Fisher
authors.affiliation: Department of Epidemiology, Michigan State University, East Lansing, MI, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Anthony
authors.affiliation: 1] Department of Family and Community Health, University of Maryland School of Nursing, Baltimore, MD, USA [2] Department of Psychiatry and Center for Nicotine and Smoking Cessation Research, Duke University, Durham NC, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Storr
authors.affiliation: Department of Psychiatry and Center for Nicotine and Smoking Cessation Research, Duke University, Durham NC, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Behm
authors.affiliation: Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Eaton
authors.affiliation: Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ialongo
authors.affiliation: Department of Psychiatry and Center for Nicotine and Smoking Cessation Research, Duke University, Durham NC, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Rose
mesh_terms: D000293:Adolescent; D001552:Benzazepines / Q000627:therapeutic use; D016642:Bupropion / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage; D017063:Outcome Assessment, Health Care; D020641:Polymorphism, Single Nucleotide; D011810:Quinoxalines / Q000627:therapeutic use; D015203:Reproducibility of Results; D012307:Risk Factors; D016540:Smoking Cessation; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D061485:Tobacco Use Cessation Devices; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000517:prevention & control; D000068580:Varenicline; D055815:Young Adult
chemical_list: D001552:Benzazepines; D011810:Quinoxalines; D016642:Bupropion; D009538:Nicotine; D000068580:Varenicline