Program Goals and Scope. Tobacco use is the foremost cause of premature death in the U.S. About 21% of adults are current smokers and smoking rates have not declined in recent years. Although available pharmacotherapies can aid in quitting smoking, quit rates vary substantially in subgroups of smokers. Thus, smoking is a significant clinical problem with a great need for research to improve treatment outcomes. The goal of the Pharmacogenetics of Nicotine Addiction Treatment (PNAT) research program is to generate the evidence base to optimize pharmacotherapeutic choices for individuals who wish to quit smoking. Building upon a strong foundafion of translafional pharmacogenefic (PGx) science conducted by this transdiscipiinary team during the past 4 vears. we propose in this competing renewal to: (a) conduct a multi-center prospective stratified PGx clinical trial to establish the predictive validity and cost-effectiveness of a genetically-informed biomarker to optimize smoking cessation treatment; (b) identify additional gene variants altering nicotine pharmacokinetics (PK), as well as pharmacodynamic (PD) gene variants influencing therapeutic response; and (c) elucidate causal mechanisms underiying associations of our PGx marker with smoking cessation.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZRG1-GGG-M)
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University of Pennsylvania
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Peng, Annie R; Schnoll, Robert; Hawk Jr, Larry W et al. (2018) Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes. Drug Alcohol Depend 190:72-81
Taghavi, Taraneh; Novalen, Maria; Lerman, Caryn et al. (2018) A Comparison of Direct and Indirect Analytical Approaches to Measuring Total Nicotine Equivalents in Urine. Cancer Epidemiol Biomarkers Prev 27:882-891
Chenoweth, Meghan J; Ware, Jennifer J; Zhu, Andy Z X et al. (2018) Genome-wide association study of a nicotine metabolism biomarker in African American smokers: impact of chromosome 19 genetic influences. Addiction 113:509-523
Tanner, Julie-Anne; Zhu, Andy Z; Claw, Katrina G et al. (2018) Novel CYP2A6 diplotypes identified through next-generation sequencing are associated with in-vitro and in-vivo nicotine metabolism. Pharmacogenet Genomics 28:7-16
Barr, Mera S; Rajji, Tarek K; Zomorrodi, Reza et al. (2017) Impaired theta-gamma coupling during working memory performance in schizophrenia. Schizophr Res 189:104-110
Peng, Annie R; Morales, Mark; Wileyto, E Paul et al. (2017) Measures and predictors of varenicline adherence in the treatment of nicotine dependence. Addict Behav 75:122-129
Li, Sufang; Yang, Yihong; Hoffmann, Ewa et al. (2017) CYP2A6 Genetic Variation Alters Striatal-Cingulate Circuits, Network Hubs, and Executive Processing in Smokers. Biol Psychiatry 81:554-563
Taghavi, Taraneh; St Helen, Gideon; Benowitz, Neal L et al. (2017) Effect of UGT2B10, UGT2B17, FMO3, and OCT2 genetic variation on nicotine and cotinine pharmacokinetics and smoking in African Americans. Pharmacogenet Genomics 27:143-154
Tanner, Julie-Anne; Henderson, Jeffrey A; Buchwald, Dedra et al. (2017) Variation in CYP2A6 and nicotine metabolism among two American Indian tribal groups differing in smoking patterns and risk for tobacco-related cancer. Pharmacogenet Genomics 27:169-178
Ware, Jennifer J; Tanner, Julie-Anne; Taylor, Amy E et al. (2017) Does coffee consumption impact on heaviness of smoking? Addiction 112:1842-1853

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