This project aims to increase our understanding of the etiology, development, heterogeneity and comorbidity of smoking by examining both individual and contextual influences. It focuses on adolescents, who are at greatest risk for smoking initiation (SI) and in whom prevention and control of smoking persistence (SP) would have the greatest potential benefit to public health. The last decade has seen tremendous growth in quantitative statistical methods for complex traits, and in large genetically informative epidemiological samples, which now allow us to test critical complex questions. We have access to three longitudinal genetically informative data sets of adolescent twins and their parents, six data sets with published adolescent smoking data and three extended twin (ET) kinship studies. Detailed data on smoking behavior are available in one adult and in three adolescent/young adult twin samples. Data are from the United States, Belgium, the Netherlands, Finland, Australia and Sweden. We will test the following hypotheses about SI: 1) SI in early adolescence is primarily influenced by shared environmental factors;genetic factors gradually contribute more to liability to SI in later adolescence and young adulthood, 2) the rates of SI vary by culture (US, Europe, Australia), but variance components do not, 3) the influence of parents and parental smoking decreases and that of siblings and peers increases from adolescence to young adulthood, 4) the influence of measured environmental factors gradually decreases and that of measured genes (identified in GWAS) increases over adolescence, 5) the effect of measured genes on SI varies as a function of environmental factors (GxE), 6) the role of genes and environment is the same for males and females. The second set of hypotheses concerns the relationship between SI and SP/ nicotine dependence (ND). We will test whether 7) there is significant but not complete genetic and environmental overlap between SI and measures of SP &ND in adolescence/ young adulthood, 8) there is significant measurement variance by age and sex for SP/ND, 9) the same genes and environments influence SI and SP throughout adolescence, 10) there is genetic overlap between SI, age of onset of SI and between age of onset and SP/ND, 11) the contribution of environmental risk factors is greater to SI than to SP/ND, and 12) the contribution of measured genes (identified in GWAS) is greater for SP/ND than for SI. Our access to rich developmental (prospective and retrospective) data sets and our expertise in statistical modeling of genetically informative samples, puts us in a unique and ideal position to address these specific aims. Doing so will substantially improve understanding of how nature and nurture interact to generate liability to smoking.

Public Health Relevance

This project aims to increase our understanding of the etiology, development, heterogeneity and comorbidity of smoking, which remains the leading preventable cause of death in the US, accounting for approximately 1 or ever 5 deaths. We will focus on both individual and contextual influences in order to make progress in prevention and control of smoking behavior, and thus influence public health.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Kimmel, Heather L
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Virginia Commonwealth University
Schools of Medicine
United States
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Maes, Hermine H; Morley, Kate; Neale, Michael C et al. (2018) Cross-Cultural Comparison of Genetic and Cultural Transmission of Smoking Initiation Using an Extended Twin Kinship Model. Twin Res Hum Genet 21:179-190
Gillespie, Nathan A; Neale, Michael C; Bates, Timothy C et al. (2018) Testing associations between cannabis use and subcortical volumes in two large population-based samples. Addiction :
Do, Elizabeth K; Prom-Wormley, Elizabeth C; Fuemmeler, Bernard F et al. (2018) Associations Between Initial Subjective Experiences with Tobacco and Self-Reported Recent Use in Young Adulthood. Subst Use Misuse 53:2291-2298
Sawdey, Michael D; Hancock, Linda; Messner, Marcus et al. (2017) Assessing the Association Between E-Cigarette Use and Exposure to Social Media in College Students: A Cross-Sectional Study. Subst Use Misuse 52:1910-1917
Maes, Hermine H; Prom-Wormley, Elizabeth; Eaves, Lindon J et al. (2017) A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents. Nicotine Tob Res 19:401-409
Do, Elizabeth K; Maes, Hermine H (2017) Genotype × Environment Interaction in Smoking Behaviors: A Systematic Review. Nicotine Tob Res 19:387-400
Prom-Wormley, Elizabeth C; Ebejer, Jane; Dick, Danielle M et al. (2017) The genetic epidemiology of substance use disorder: A review. Drug Alcohol Depend 180:241-259
Verhulst, Brad; Maes, Hermine H; Neale, Michael C (2017) GW-SEM: A Statistical Package to Conduct Genome-Wide Structural Equation Modeling. Behav Genet 47:345-359
Maes, Hermine H; Neale, Michael C; Ohlsson, Henrik et al. (2016) A Bivariate Genetic Analysis of Drug Abuse Ascertained Through Medical and Criminal Registries in Swedish Twins, Siblings and Half-Siblings. Behav Genet 46:735-741
Do, Elizabeth; Maes, Hermine (2016) Narrative review of genes, environment, and cigarettes. Ann Med 48:337-51

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