Through this K08 application, I request support to facilitate my transition to an independent researcher in statistical genetics as applied to nicotin dependence and comorbid psychiatric disorders. I have a foundation both in statistics and clinical psychiatry, and recent postdoctoral training in psychiatric and addiction genetics. This grant will provide me with the additional training I need in statistical genetics, data collection, grant development, and project management. Using a combination of didactic coursework and supervision with mentors in quantitative genetics (Drs. James Cheverud, and Peter Kraft), addiction genetics (Dr. Laura Bierut), molecular genetics (Dr. Alison Goate), and psychiatric genetics (Dr. Michael Owen), I will develop the expertise needed to become a successful, independent investigator. The research proposed in this application was designed to significantly contribute to the field of addiction genetics, and to complement my career development plan by leveraging the skills of my mentors to help guide me to develop an independent field of study. The three aims are (1) to calculate the proportion of phenotypic variance for nicotine dependence that is explained by the common SNPs in genome-wide association studies (GWAS) to better understand the total amount of information available in the datasets, (2) to examine homogenous subgroups of individuals and compare contrasting subgroups of individuals to find novel loci that are more strongly associated with nicotine dependence, particularly in the context of comorbid psychiatric disorders, and (3) to develop a database to maximize power for discovery of genetic variants that contribute to nicotine dependence. These studies will help me to develop a strong research program that uses my unique combination of quantitative expertise with clinical knowledge to better understand the genetics of smoking and comorbid psychiatric disorders.

Public Health Relevance

Nicotine dependence and smoking continue to be the leading cause of preventable death worldwide. In particular, individuals with other psychiatric disorders including bipolar disorder, schizophrenia, and depression are particularly at risk for the development of dependence and the associated medical risks. The proposed application aims to both solidify our understanding of how genetics contributes to the disorders and investigate whether there are overlapping genetic risk factors for the development of both nicotine dependence and other psychiatric disorders. The results of this study will lead to improved understanding and treatment of these disorders.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Clinical Investigator Award (CIA) (K08)
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Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Wanke, Kay
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Washington University
Schools of Medicine
Saint Louis
United States
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Hartz, Sarah M; Horton, Amy C; Hancock, Dana B et al. (2018) Genetic correlation between smoking behaviors and schizophrenia. Schizophr Res 194:86-90
Hartz, Sarah M; Oehlert, Mary; Horton, A C et al. (2018) Daily Drinking Is Associated with Increased Mortality. Alcohol Clin Exp Res 42:2246-2255
Olfson, Emily; Bloom, Joseph; Bertelsen, Sarah et al. (2018) CYP2A6 metabolism in the development of smoking behaviors in young adults. Addict Biol 23:437-447
Hartz, Sarah M; Horton, Amy C; Oehlert, Mary et al. (2017) Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia. Biol Psychiatry 82:709-715
Chen, Li-Shiun; Baker, Timothy; Brownson, Ross C et al. (2017) Smoking Cessation and Electronic Cigarettes in Community Mental Health Centers: Patient and Provider Perspectives. Community Ment Health J 53:695-702
Estrada, Elena; Hartz, Sarah M; Tran, Jeffrey et al. (2016) Nicotine dependence and psychosis in Bipolar disorder and Schizoaffective disorder, Bipolar type. Am J Med Genet B Neuropsychiatr Genet 171:521-4
Olfson, E; Saccone, N L; Johnson, E O et al. (2016) Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans. Mol Psychiatry 21:601-7
Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun et al. (2016) Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Behav Genet 46:151-69
Olfson, Emily; Hartz, Sarah; Carere, Deanna Alexis et al. (2016) Implications of Personal Genomic Testing for Health Behaviors: The Case of Smoking. Nicotine Tob Res 18:2273-2277
Hartz, Sarah M; Olfson, Emily; Culverhouse, Robert et al. (2015) Return of individual genetic results in a high-risk sample: enthusiasm and positive behavioral change. Genet Med 17:374-9

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