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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DA032680-02
Application #
8469460
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Kimmel, Heather L
Project Start
2012-05-15
Project End
2017-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$137,458
Indirect Cost
$10,182
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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
Hartz, Sarah M; Pato, Carlos N; Medeiros, Helena et al. (2014) Comorbidity of severe psychotic disorders with measures of substance use. JAMA Psychiatry 71:248-54
Agrawal, Arpana; Lynskey, Michael T; Bucholz, Kathleen K et al. (2014) DSM-5 cannabis use disorder: a phenotypic and genomic perspective. Drug Alcohol Depend 134:362-9
Stephens, Sarah H; Hartz, Sarah M; Hoft, Nicole R et al. (2013) Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking. Genet Epidemiol 37:846-59