Nicotine abstinence genotyping: assessing the impact on smoking cessation clinical trials

Nicotine abstinence genotyping: assessing the impact on smoking cessation clinical trials


Play all audios:


Original Article Published: 09 September 2008 Nicotine abstinence genotyping: assessing the impact on smoking cessation clinical trials G R Uhl1, T Drgon1, C Johnson1 & …J E Rose2 Show


authors The Pharmacogenomics Journal volume 9, pages 111–115 (2009)Cite this article


436 Accesses


14 Citations


Metrics details

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 model the effects


of genotypic stratification in smoking cessation trials. We identify relationships between the costs of identifying and genotyping prospective trial participants vs the costs of performing


the clinical trials. We quantitate the increasing savings that result from genetically stratified designs as recruiting/genotyping costs go down and trial costs increase. 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 institution Buy or subscribe This is a preview of subscription content, access via your institution


Access options Access through your institution Additional access options: Log in Learn about institutional subscriptions Read our FAQs Contact customer support Figure 1Figure 2 Similar


content 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 informationAuthors 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


AuthorsG R UhlView author publications You can also search for this author inPubMed Google Scholar


T DrgonView author publications You can also search for this author inPubMed Google Scholar


C JohnsonView author publications You can also search for this author inPubMed Google Scholar


J E RoseView 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 articleCite 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 able to read this content:


Get shareable link Sorry, a shareable link is not currently available for this article.


Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative


Keywordsclinical trial powerpharmacogenomicspharmacogeneticsnicotine dependencepharmacotherapiesaddiction This article is cited by Smoking quit success genotype score predicts quit success


and distinct patterns of developmental involvement with common addictive substances G R UhlD WaltherJ E Rose Molecular Psychiatry (2014)


Biomarkers for Smoking Cessation K J BoughC LermanS Amur Clinical Pharmacology & Therapeutics (2013)


Genetics of dopamine receptors and drug addiction Philip GorwoodYann Le StratMichel Simonneau Human Genetics (2012)


Early Human Screening of Medications to Treat Drug Addiction: Novel Paradigms and the Relevance of Pharmacogenetics K A PerkinsC Lerman Clinical Pharmacology & Therapeutics (2011)