This project will test genetic risk markers for smoking trajectory from adolescence through young adulthood in a cohort collected during the initial program project. We will concentrate on genetic risk markers in neuronal nicotinic acetylcholine receptors (nAChRs) but also will consider a limited number of other candidate genes for which there is strong empirical support. We reported previously that CHRNA5-A3-B4 haplotype association with adult nicotine dependence in Whites was more robust in smokers who began daily smoking prior to age 17. This strongly suggests a heightened sensitivity to these risk markers in adolescents. This project uses a unique, prospectively studied adolescent cohort with a rich set of longitudinal phenotypes characterizing smoking progression. We will test possible additive and Interactive effects of genetic risk markers and other variables known to be associated with smoking trajectory (e.g., gender, race, substance use, depression, peer influence and parental smoking). Also, we will examine hypotheses regarding the mediation of genetic associations with smoking trajectoiy by short-term affect regulation and alleviation of nicotine withdrawal by cigarette smoking. Further, we will determine the genetic architecture of nAChR genes within the racial/ethnic groups represented in the study cohort so haplotype-specific genetic risk markers can be tested across races.

Public Health Relevance

Adolescence and young adulthood Is the time of highest risk of becoming nicotine dependent. This project will examine the contribution of genetics to the progression of nicotine dependence and will assess how genetic and non-genetic factors combine to affect risk for nicotine dependence. Results of this research will contribute to more effective smoking prevention and cessation programs in the future.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-7)
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University of Illinois at Chicago
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Dierker, Lisa; Rose, Jennifer; Selya, Arielle et al. (2015) Depression and nicotine dependence from adolescence to young adulthood. Addict Behav 41:124-8
Nadell, Melanie J; Mermelstein, Robin J; Hedeker, Donald et al. (2015) Work and Non-Work Physical Activity Predict Real-Time Smoking Level and Urges in Young Adults. Nicotine Tob Res 17:803-9
Hedeker, Donald (2015) Methods for Multilevel Ordinal Data in Prevention Research. Prev Sci 16:997-1006
Coon, Hilary; Piasecki, Thomas M; Cook, Edwin H et al. (2014) Association of the CHRNA4 neuronal nicotinic receptor subunit gene with frequency of binge drinking in young adults. Alcohol Clin Exp Res 38:930-7
Pugach, Oksana; Hedeker, Donald; Mermelstein, Robin (2014) A Bivariate Mixed-Effects Location-Scale Model with application to Ecological Momentary Assessment (EMA) data. Health Serv Outcomes Res Methodol 14:194-212
Pugach, Oksana; Hedeker, Donald; Richmond, Melanie J et al. (2014) Modeling mood variation and covariation among adolescent smokers: application of a bivariate location-scale mixed-effects model. Nicotine Tob Res 16 Suppl 2:S151-8
Cannon, Dale S; Mermelstein, Robin J; Hedeker, Donald et al. (2014) Effect of neuronal nicotinic acetylcholine receptor genes (CHRN) on longitudinal cigarettes per day in adolescents and young adults. Nicotine Tob Res 16:137-44
Mermelstein, Robin J (2014) Adapting to a changing tobacco landscape: research implications for understanding and reducing youth tobacco use. Am J Prev Med 47:S87-9
Piasecki, Thomas M; Trela, Constantine J; Hedeker, Donald et al. (2014) Smoking antecedents: separating between- and within-person effects of tobacco dependence in a multiwave ecological momentary assessment investigation of adolescent smoking. Nicotine Tob Res 16 Suppl 2:S119-26
Sokolovsky, Alexander W; Mermelstein, Robin J; Hedeker, Donald (2014) Factors predicting compliance to ecological momentary assessment among adolescent smokers. Nicotine Tob Res 16:351-8

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