Grant Number:	5R21CA226300-02 Interpret this number
Primary Investigator:	Kamens, Helen
Organization:	Pennsylvania State University, The
Project Title:	The Moderating Role of Smoking Exposure in the Relationship Between the Nicotinic Acetylcholine Receptor Gene Cluster and Nicotine Dependence
Fiscal Year:	2021

Project Summary/Abstract Progress in our ability to evaluate the interaction between genetic effects and environmental factors in understanding risk for nicotine dependence has been significantly impeded by inadequate single study sample sizes and meta analyses that are necessarily limited to the estimation of effect sizes for research questions that have been previously addressed within single studies. Fortunately, recent methodological innovations now permit the combination of data sets that differ in terms of study design, populations, and measures. This integrative data analysis (IDA) allows us to pool the raw data from multiple studies, allowing us to test new hypotheses and results in more powerful, more comprehensive, and more rigorous studies than we achieve through analysis of single studies or by using traditional meta analytic techniques. The present research will combine both an innovative approach (IDA) and innovative statistical methods (moderated nonlinear factor analysis; MNLFA and time-varying effects models; TVEM), to evaluate the association between genetic variants in the CHRNA5/CHRNA3/CHRNB4 and CHRNA6/CHRNB3 regions and nicotine dependence symptoms across levels of smoking exposure. Taking advantage of existing resources, we will pool extant data from the Social Emotional Contexts of Adolescent Smoking Project (SECASP), The National Longitudinal Study of Adolescent Health (AddHealth), the National Youth Survey Family Study (NYSFS) and the Study of Addiction: Genetics and Environment (SAGE) to evaluate changes in the association between SNPs in the acetylcholine receptor gene clusters and an empirically harmonized nicotine dependence score across levels of smoking exposure and to estimate the additional contribution of timing of smoking exposure in explaining the association between individual genetic variants and nicotine dependence symptoms. The innovative methods of data integration with MNLFA will allow us to begin to explore exposure varying effects in an extremely cost-effective manner in that we will leverage previous investment in tracking, contacting, assessing, and collecting DNA from 4 large studies assessing adolescents and adults. The empirically based nicotine dependence symptom score derived from the cross-study MNLFA model will provide a much more sensitive measure of the nicotine dependence phenotype than traditional methods of scoring within study, and one that is uniquely harmonized to account for between study differences.




Cigarette dependence is more prevalent and increasing among US adolescents and adults who use cannabis, 2002-2019.
Authors: Weinberger A.H. , Dierker L. , Zhu J. , Levin J. , Goodwin R.D. .
Source: Tobacco control, 2023 Jul; 32(4), p. 443-449.
EPub date: 2021-11-23.
PMID: 34815363
Related Citations

The role of nicotinic receptors in alcohol consumption.
Authors: Kamens H.M. , Flarend G. , Horton W.J. .
Source: Pharmacological research, 2023 Apr; 190, p. 106705.
EPub date: 2023-02-20.
PMID: 36813094
Related Citations

The effect of stress on opioid addiction-related behaviors: A review of preclinical literature.
Authors: Kamens H.M. , Flarend G. , Wickenheisser A. , Horton W.J. , Cavigelli S.A. .
Source: Experimental and clinical psychopharmacology, 2023 Apr; 31(2), p. 523-540.
EPub date: 2022-07-14.
PMID: 35834183
Related Citations

The impact of adolescent stress on nicotine use and affective disorders in rodent models.
Authors: Mooney-Leber S.M. , Caruso M.J. , Gould T.J. , Cavigelli S.A. , Kamens H.M. .
Source: The European journal of neuroscience, 2022 May; 55(9-10), p. 2196-2215.
EPub date: 2021-08-30.
PMID: 34402112
Related Citations

Covariate Information Number for Feature Screening in Ultrahigh-Dimensional Supervised Problems.
Authors: Nandy D. , Chiaromonte F. , Li R. .
Source: Journal of the American Statistical Association, 2022; 117(539), p. 1516-1529.
EPub date: 2021-02-10.
PMID: 36172297
Related Citations

Cigarette smoke-induced alterations in blood: A review of research on DNA methylation and gene expression.
Authors: Silva C.P. , Kamens H.M. .
Source: Experimental and clinical psychopharmacology, 2021 Feb; 29(1), p. 116-135.
EPub date: 2020-07-13.
PMID: 32658533
Related Citations

Alcohol Use Disorder Symptoms Rather than Alcohol Exposure Predict Experiences of Cannabis Use Disorder Symptoms among Adolescents and Young Adults.
Authors: Dierker L.C. , Selya A.S. .
Source: Substance use & misuse, 2021; 56(3), p. 431-435.
EPub date: 2021-01-11.
PMID: 33427539
Related Citations