ABSTRACT Twin studies document substantial heritability for successful abstinence from smoking. A genome-wide association study has identified markers whose allele frequencies differ with

nominal _P_<0.005 in nicotine-dependent clinical trial participants who were successful vs unsuccessful in abstaining from smoking; many of these results are also supported by data from

two additional samples. More study is required to precisely determine the variance in quitting success that can be accounted for by the single-nucleotide polymorphisms that are currently

identified and to precisely classify individuals who may display varying degrees of genetic vs environmental effects into quitters or nonquitters. However, the data at hand do allow us to

This model helps to define the circumstances in which genetically stratified designs may enhance power and reduce costs for smoking cessation clinical trials. Access through your

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BEING VIEWED BY OTHERS DEEP SEQUENCING OF CANDIDATE GENES IDENTIFIED 14 VARIANTS ASSOCIATED WITH SMOKING ABSTINENCE IN AN ETHNICALLY DIVERSE SAMPLE Article Open access 16 March 2024

EXPANDING THE GENETIC ARCHITECTURE OF NICOTINE DEPENDENCE AND ITS SHARED GENETICS WITH MULTIPLE TRAITS Article Open access 03 November 2020 GENOME-WIDE ASSOCIATION STUDY OF SMOKING

TRAJECTORY AND META-ANALYSIS OF SMOKING STATUS IN 842,000 INDIVIDUALS Article Open access 20 October 2020 REFERENCES * Uhl GR, Elmer GI, Labuda MC, Pickens RW . Genetic influences in drug

abuse. In: Gloom FE, Kupfer DJ (eds). _Psychopharmacology: The Fourth Generation of Progress_. Raven Press: New York, 1995, pp 1793–2783. Google Scholar  * Tsuang MT, Lyons MJ, Meyer JM,

Doyle T, Eisen SA, Goldberg J _et al_. Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities. _Arch Gen Psychiatry_ 1998; 55: 967–972.

Article  CAS  PubMed  Google Scholar  * Karkowski LM, Prescott CA, Kendler KS . Multivariate assessment of factors influencing illicit substance use in twins from female-female pairs. _Am J

Med Genet_ 2000; 96: 665–670. Article  CAS  PubMed  Google Scholar  * True WR, Heath AC, Scherrer JF, Xian H, Lin N, Eisen SA _et al_. Interrelationship of genetic and environmental

influences on conduct disorder and alcohol and marijuana dependence symptoms. _Am J Med Genet_ 1999; 88: 391–397. Article  CAS  PubMed  Google Scholar  * Xian H, Scherrer JF, Madden PA,

Lyons MJ, Tsuang M, True WR _et al_. The heritability of failed smoking cessation and nicotine withdrawal in twins who smoked and attempted to quit. _Nicotine Tob Res_ 2003; 5: 245–254.

Article  CAS  PubMed  Google Scholar  * Broms U, Silventoinen K, Madden PA, Heath AC, Kaprio J . Genetic architecture of smoking behavior: a study of Finnish adult twins. _Twin Res Hum

Genet_ 2006; 9: 64–72. Article  PubMed  Google Scholar  * Carmelli D, Swan GE, Robinette D, Fabsitz R . Genetic influence on smoking—a study of male twins. _N Engl J Med_ 1992; 327: 829–833.

Article  CAS  PubMed  Google Scholar  * Morley KI, Lynskey MT, Madden PA, Treloar SA, Heath AC, Martin NG . Exploring the inter-relationship of smoking age-at-onset, cigarette consumption

and smoking persistence: genes or environment? _Psychol Med_ 2007; 37: 1357–1367. Article  PubMed  Google Scholar  * Tonnesen P, Norregaard J, Simonsen K, Sawe U . A double-blind trial of a

16-h transdermal nicotine patch in smoking cessation. _N Engl J Med_ 1991; 325: 311–315. Article  CAS  PubMed  Google Scholar  * Kenford SL, Fiore MC, Jorenby DE, Smith SS, Wetter D, Baker

TB . Predicting smoking cessation. Who will quit with and without the nicotine patch. _JAMA_ 1994; 271: 589–594. Article  CAS  PubMed  Google Scholar  * Jones RL, Nguyen A, Man SF . Nicotine

and cotinine replacement when nicotine nasal spray is used to quit smoking. _Psychopharmacology (Berl)_ 1998; 137: 345–350. Article  CAS  Google Scholar  * Uhl GR, Liu QR, Drgon T, Johnson

C, Walther D, Rose JE . Molecular genetics of nicotine dependence and abstinence: whole genome association using 520 000 SNPs. _BMC Genet_ 2007; 8: 10. Article  PubMed  PubMed Central 

Google Scholar  * Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE _et al_. Molecular genetics of successful smoking cessation: convergent genome-wide association study results. _Arch

Gen Psychiatry_ 2008; 65: 683–693. Article  CAS  PubMed  PubMed Central  Google Scholar  * Cornuz J, Gilbert A, Pinget C, McDonald P, Slama K, Salto E _et al_. Cost-effectiveness of

pharmacotherapies for nicotine dependence in primary care settings: a multinational comparison. _Tob Control_ 2006; 15: 152–159. Article  CAS  PubMed  PubMed Central  Google Scholar  * Hall

SM, Lightwood JM, Humfleet GL, Bostrom A, Reus VI, Munoz R . Cost-effectiveness of bupropion, nortriptyline, and psychological intervention in smoking cessation. _J Behav Health Serv Res_

2005; 32: 381–392. Article  PubMed  Google Scholar  * Hughes JR, Giovino GA, Klevens RM, Fiore MC . Assessing the generalizability of smoking studies. _Addiction_ 1997; 92: 469–472. Article

  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We acknowledge the support given by the NIH IRP (NIDA), DHSS, unrestricted support for studies of adult smoking cessation

to the Duke Center for Nicotine and Smoking Cessation Research from Philip Morris USA Inc. and advice on the article and statistical approaches from Dr Greg Samsa. AUTHOR INFORMATION AUTHORS

AND AFFILIATIONS * Molecular Neurobiology Branch, NIH-IRP, NIDA, Baltimore, MD, USA G R Uhl, T Drgon & C Johnson * Department of Psychiatry and Behavioral Sciences, Center for Nicotine

and Smoking Cessation Research, Duke University, Durham, NC, USA J E Rose Authors * G R Uhl View author publications You can also search for this author inPubMed Google Scholar * T Drgon

View author publications You can also search for this author inPubMed Google Scholar * C Johnson View author publications You can also search for this author inPubMed Google Scholar * J E

Rose View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to G R Uhl. ADDITIONAL INFORMATION DUALITY OF INTEREST None

declared. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Uhl, G., Drgon, T., Johnson, C. _et al._ Nicotine abstinence genotyping: assessing the impact

on smoking cessation clinical trials. _Pharmacogenomics J_ 9, 111–115 (2009). https://doi.org/10.1038/tpj.2008.10 Download citation * Received: 18 April 2007 * Revised: 21 May 2008 *

Accepted: 03 July 2008 * Published: 09 September 2008 * Issue Date: April 2009 * DOI: https://doi.org/10.1038/tpj.2008.10 SHARE THIS ARTICLE Anyone you share the following link with will be

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initiative KEYWORDS * clinical trial power * pharmacogenomics * pharmacogenetics * nicotine dependence * pharmacotherapies * addiction