The long-range objective of this Program Project is to engender a better understanding of the factors that contribute to heightened susceptibility to smoking and nicotine dependence, using a Nicotine Research Consortium as the vehicle for coordinating and sustaining research activity derived from several independent NIH projects.
Specific aims are (a) to identify highly heritable, latent factors (endophenotypes) to characterize the course and causes of smoking behavior more accurately; (b) to use twin genetic methods to estimate the heritability (proportion of variance accounted for)of endophenotypes; and (c) to test endophenotypes for association with particular candidate genes. Systematic investigations will be carried out using both biometric and measured genetic approaches in the context of three related projects: Project A. Behavioral genetics of nicotine reactivity, will attempt to quantify the genetic contribution to nicotine-dependent smoking in concordant and discordant (monozygotic and dizygotic; MZ/DZ) twins and their siblings, focusing on initial sensitivity to nicotine and chronic tolerance as phenotypic indicators. Project B, Behavioral phenotypes and environmentalfactors for tobacco use,examines the contribution of genetic and environmental sources of variation for smoking along dimensions of dependence, lifetime tobacco use milestones and trajectories, and composite phenotypes in a series of psychometric studies and behavior genetic studies in concordant and discordant MZ/DZ twins, in order to identify endophenotypes. Project C. Candidate genesfor smoking in related and unrelated individuals, will involve an examination of -60 susceptibility genes for smoking in (a) unrelated smokers and never-smokers using a case-control design and (b) in smokers and their biological parents using a parent-child trio design to determine genetic association with endophenotypes identified in Projects A and B. Three cores support the activities of the projects: The Administrative Core, the coordinating center for the Nicotine Research Consortium, is responsible for communication, integration, and quality control. The Analytical Chemistry Core will conduct analyses of biological samples (nicotine, cotinine, hydroxy-cotinine) from each project. The Data Management and Analysis Core will provide organized statistical design, warehousing of phenotype and genotype data, and advanced genetic analyses. Health relatedness. The proposed Program Project constitutes a systematic investigation of how individual biological, behavioral, and environmental factors come together and interact to create tobacco dependence. Identification of environmental and behavioral risk factors and more accurate characterization of phenotypes and genotypes for smoking constitute crucial next steps in the elucidation of underlying mechanisms for smoking. Such knowledge will confer new insights about the etiology and progression of smoking and should improve the current understanding of smoking, which is still largely descriptive.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Application #
Study Section
Special Emphasis Panel (ZDA1-MXG-S (26))
Program Officer
Wideroff, Louise
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Sri International
Menlo Park
United States
Zip Code
Lessov-Schlaggar, Christina N; Wahlgren, Dennis R; Liles, Sandy et al. (2011) Sensitivity to secondhand smoke exposure predicts smoking susceptibility in 8-13-year-old never smokers. J Adolesc Health 48:234-40
Lessov-Schlaggar, Christina N; Wahlgren, Dennis R; Liles, Sandy et al. (2011) Sensitivity to secondhand smoke exposure predicts future smoking susceptibility. Pediatrics 128:254-62
Hovell, Melbourne F; Wahlgren, Dennis R; Liles, Sandy et al. (2011) Providing coaching and cotinine results to preteens to reduce their secondhand smoke exposure: a randomized trial. Chest 140:681-689
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Javitz, Harold S; Brigham, Janet; Lessov-Schlaggar, Christina N et al. (2009) Association of tobacco dependence and quit attempt duration with Rasch-modeled withdrawal sensitivity using retrospective measures. Addiction 104:1027-35
Lessov-Schlaggar, Christina N; Pergadia, Michele L; Khroyan, Taline V et al. (2008) Genetics of nicotine dependence and pharmacotherapy. Biochem Pharmacol 75:178-95
Brigham, Janet; Lessov-Schlaggar, Christina N; Javitz, Harold S et al. (2008) Reliability of adult retrospective recall of lifetime tobacco use. Nicotine Tob Res 10:287-99

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