In this mentored scientist development award for Dr. Xiangning Chen, sponsored by Dr. Kenneth Kendler, describes a 5-year, comprehensive training and research program for the genetics of nicotine, alcohol and other abused substances. Tobacco smoking, alcoholism and drug abuses are serious public health issues. Epidemiology studies have shown that genetics influences the behaviors of substance uses. However, the nature of these genetic factors remains largely unknown. The identification and characterization of these genetic factors would facilitate the prevention, diagnosis and treatment of substance abusers and/or dependents. In the program, four specific aims are proposed to facilitate professional growth and to cultivate independent research in the fields of substance abuse and behavioral genetics.
The aims are: 1). To use bioinformatic tools and software to select, rank and prioritize candidate genes from linkage, microarray, pharmacology and animal model and behavioral studies;2).To use a case-control sample selected from the Virginia Twin Registry to identify genetic risk factors for nicotine dependence, alcohol dependence and other substance use disorders;3). To verify risk factors identified from aim 2 with a new case-control sample collected for alcohol dependence studies;and 4). To genotype those positive markers for the cotwins of subjects used in aim 2 and to use structural equation modeling and other statistical techniques to test if genetic risk factors identified in aims 2 and 3 are specific to each substance or shared between different substances. The training components focus on bioinformatics skills, statistical principles and methods, neural chemistry and pharmacology of abused substances and classification and diagnosis of substance abuse symptoms. The proposal integrates the training activities with the research plan to achieve the goal of independent research in the fields of drug abuse genetics.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DA019498-04
Application #
7686098
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Caulder, Mark
Project Start
2006-09-11
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
4
Fiscal Year
2009
Total Cost
$168,742
Indirect Cost
Name
Virginia Commonwealth University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
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
Jackson, K J; Wang, J B; Barbier, E et al. (2013) The histidine triad nucleotide binding 1 protein is involved in nicotine reward and physical nicotine withdrawal in mice. Neurosci Lett 550:129-33
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
Kendler, Kenneth S; Myers, John; Damaj, M Imad et al. (2013) Early smoking onset and risk for subsequent nicotine dependence: a monozygotic co-twin control study. Am J Psychiatry 170:408-13
Jackson, K J; Wang, J B; Barbier, E et al. (2012) Acute behavioral effects of nicotine in male and female HINT1 knockout mice. Genes Brain Behav 11:993-1000
Hartz, Sarah M; Short, Susan E; Saccone, Nancy L et al. (2012) Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers. Arch Gen Psychiatry 69:854-60
Kendler, Kenneth S; Chen, Xiangning; Dick, Danielle et al. (2012) Recent advances in the genetic epidemiology and molecular genetics of substance use disorders. Nat Neurosci 15:181-9
Jackson, K J; Chen, Q; Chen, J et al. (2011) Association of the histidine-triad nucleotide-binding protein-1 (HINT1) gene variants with nicotine dependence. Pharmacogenomics J 11:251-7
Chen, Jingchun; Brunzell, Darlene H; Jackson, Kia et al. (2011) ACSL6 is associated with the number of cigarettes smoked and its expression is altered by chronic nicotine exposure. PLoS One 6:e28790
Jackson, Kia J; Chen, Xiangning; Miles, Michael F et al. (2011) The neuropeptide galanin and variants in the GalR1 gene are associated with nicotine dependence. Neuropsychopharmacology 36:2339-48

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