This proposed R01 constitutes a collaboration among three ongoing longitudinal studies: the Seattle Social Development Project (SSDP, Karl G. Hill, PI), the Raising Healthy Children Project (RHC, Richard F. Catalano, PI) and projects from the Minnesota Center for Twin and Family Research (MCTFR, Matthew McGue, and William Iacono, PIs). To lay the foundation for the proposed study, work to be completed under the current twoyear ARRA grant has permitted SSDP to (1) create measures of addiction phenotypes and measures of the environment suitable for gene-environment (G-E) analysis, (2) test models of environment and phenotype suitable for later inclusion of genetic data, (3) collect DNA samples from the SSDP longitudinal panel and (4) conduct a whole-genome genotyping in anticipation of subsequent genetic association and G-E analyses. The proposed R01 will extend this work by conducting genetic association analyses and examining G-E interplay in the development of addiction and HIV sexual risk behavior, tasks not supported by the ARRA grant.
In Aim 1 we will utilize data from SSDP, RHC, MCTFR and three samples from the Genotypes and Phenotypes (dbGaP) archive to develop genetic system vulnerability scores for three systems related to addiction: dopamine, serotonin and GABA.
Aim 1 also examines the contribution of these genetic system vulnerability scores to HIV sexual risk behavior, illicit drug use and crime.
Aim 2 will examine mechanisms of genetic influence on addiction as well as gene-environment correlation and interaction through a test-and-replicate strategy employing SSDP, RHC and MCTFR samples.
Aim 2 also examines the extent to which these geneenvironment models predict HIV-sexual risk behavior, illicit drug use and crime.
Aim 3 will examine gene x intervention interaction (GxI), and whether the influence of genetic factors on problem outcomes can be mitigated by social developmental preventive intervention during childhood. The proposed study builds on data sets of existing comparable phenotypic, individual and environmental measures in three well-characterized, longitudinal samples. Two of the data sets (SSDP and MCTFR) already have whole-genome genotypic data, and RHC has DNA collected and ready to be genotyped. All three panels contain indicators of environmental risk factors for tobacco and alcohol use and problem use assessed multiple times from childhood to adulthood. All three panels also include assessments of DSM-IV diagnoses as well as other quantitative measures of drug abuse and dependence and related phenotypes of demonstrated heritability. Finally, both SSDP and RHC implemented a social-developmental preventive intervention with parents, teachers and children early in life, permitting examination of gene x intervention interaction. The alliance of the SSDP, RHC and MCTFR research teams provides an opportunity to learn how, at different developmental periods, environmental factors might amplify or reduce genetic vulnerability to tobacco and alcohol problems. Findings will inform the design of improved preventive and treatment interventions for these common and costly disorders.

Public Health Relevance

Drug abuse and dependence are leading causes of morbidity and mortality among adolescents and adults in the United States, and the development of drug abuse and dependence has been shown to be intertwined with HIV sexual risk behavior, crime and other problems. Vulnerability to develop these problems is influenced by a combination of environmental and genetic factors. The proposed study will improve understanding of contributions of and interactions among environmental, genetic and developmental factors in development of drug abuse and dependence, HIV sexual risk behavior and related outcomes, and its findings will provide information of use to those designing improved preventive and treatment interventions for these common and costly disorders.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Application #
Study Section
Risk, Prevention and Intervention for Addictions Study Section (RPIA)
Program Officer
Etz, Kathleen
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University of Washington
Schools of Social Work
United States
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Guttmannova, Katarina; Wheeler, Melissa J; Hill, Karl G et al. (2017) Assessment of Risk and Protection in Native American Youth: Steps Toward Conducting Culturally Relevant, Sustainable Prevention in Indian Country. J Community Psychol 45:346-362
Lee, Jungeun Olivia; Jones, Tiffany M; Kosterman, Rick et al. (2017) The association of unemployment from age 21 to 33 with substance use disorder symptoms at age 39: The role of childhood neighborhood characteristics. Drug Alcohol Depend 174:1-8
Jolliffe, Darrick; Farrington, David P; Piquero, Alex R et al. (2017) Systematic review of early risk factors for life-course-persistent, adolescence-limited, and late-onset offenders in prospective longitudinal studies. Aggress Violent Behav 33:15-23
Kristman-Valente, Allison N; Hill, Karl G; Epstein, Marina et al. (2017) The Relationship Between Marijuana and Conventional Cigarette Smoking Behavior from Early Adolescence to Adulthood. Prev Sci 18:428-438
Elizabeth Kim, B K; Gilman, Amanda B; Hill, Karl G et al. (2016) Examining Protective Factors Against Violence among High-risk Youth: Findings from the Seattle Social Development Project. J Crim Justice 45:19-25
Kosterman, Rick; Bailey, Jennifer A; Guttmannova, Katarina et al. (2016) Marijuana Legalization and Parents' Attitudes, Use, and Parenting in Washington State. J Adolesc Health 59:450-6
Szyf, Moshe; Tang, Yi-Yang; Hill, Karl G et al. (2016) The dynamic epigenome and its implications for behavioral interventions: a role for epigenetics to inform disorder prevention and health promotion. Transl Behav Med 6:55-62
Kristman-Valente, Allison N; Oesterle, Sabrina; Hill, Karl G et al. (2016) The Relationship between Interpersonal Violence Victimization and Smoking Behavior across Time and by Gender. J Soc Work Pract Addict 16:132-159
Jones, Tiffany M; Hill, Karl G; Epstein, Marina et al. (2016) Understanding the interplay of individual and social-developmental factors in the progression of substance use and mental health from childhood to adulthood. Dev Psychopathol 28:721-41
Lee, J O; Kosterman, R; Jones, T M et al. (2016) Mechanisms linking high school graduation to health disparities in young adulthood: a longitudinal analysis of the role of health behaviours, psychosocial stressors, and health insurance. Public Health 139:61-69

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