Cigarette smoking is a major risk factor for premature death and creates a substantial public health burden. While studies have shown that smoking and nicotine dependence are complex traits influenced by significant genetic components, further research is needed to identify genes that influence susceptibility and resistance. The research goal of this proposal is to develop and evaluate new methods for the genetic analysis of complex traits in the context of career development for the candidate, Dr. Nancy Saccone. Dr. Saccone will use artificial neural networks and logistic regression models as her primary methodological tools, and will develop and apply methods especially suited for studying the complex genetics of nicotine addiction and related phenotypes. Preliminary studies have been promising and indicate that further investigation of genetic methods based on these tools is warranted. The research plan will also extend the scope of these applications to include uses for genetic association analysis, as large-scale disequilibrium and association-based approaches are expected to become increasingly important for complex trait gene mapping. Dr. Saccone has chosen Dr. John Rice as mentor and will work with additional co-mentors and consultants. The training components of this proposal will expand Dr. Saccone?s experience to include: ongoing training in the ethical conduct of research, further training in the clinical and biological aspects of nicotine and other substance addiction, and the development of expertise in the use and analysis of other kinds of genetic data besides genotypic data, such as gene expression array data, which will play increasingly important roles in the study of human complex traits. The candidate has designed a program of coursework and mentoring to accomplish these research and training goals and thereby achieve research independence by the end of the award period.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DA015129-04
Application #
6864825
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Caulder, Mark
Project Start
2002-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
4
Fiscal Year
2005
Total Cost
$129,738
Indirect Cost
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Saccone, Nancy L; Saccone, Scott F; Hinrichs, Anthony L et al. (2009) Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes. Am J Med Genet B Neuropsychiatr Genet 150B:453-66
Sherva, Richard; Rice, John P; Neuman, Rosalind J et al. (2009) Associations and interactions between SNPs in the alcohol metabolizing genes and alcoholism phenotypes in European Americans. Alcohol Clin Exp Res 33:848-57
Agrawal, Arpana; Pergadia, Michele L; Balasubramanian, Sumitra et al. (2009) Further evidence for an association between the gamma-aminobutyric acid receptor A, subunit 4 genes on chromosome 4 and Fagerström Test for Nicotine Dependence. Addiction 104:471-7
Saccone, Scott F; Bierut, Laura J; Chesler, Elissa J et al. (2009) Supplementing high-density SNP microarrays for additional coverage of disease-related genes: addiction as a paradigm. PLoS One 4:e5225
Dick, Danielle M; Aliev, Fazil; Wang, Jen C et al. (2008) A Systematic single nucleotide polymorphism screen to fine-map alcohol dependence genes on chromosome 7 identifies association with a novel susceptibility gene ACN9. Biol Psychiatry 63:1047-53
Saccone, Nancy L; Saccone, Scott F; Goate, Alison M et al. (2008) In search of causal variants: refining disease association signals using cross-population contrasts. BMC Genet 9:58
Agrawal, Arpana; Pergadia, Michele L; Saccone, Scott F et al. (2008) Gamma-aminobutyric acid receptor genes and nicotine dependence: evidence for association from a case-control study. Addiction 103:1027-38
Bierut, Laura Jean; Stitzel, Jerry A; Wang, Jen C et al. (2008) Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry 165:1163-71
Saccone, Scott F; Saccone, Nancy L; Swan, Gary E et al. (2008) Systematic biological prioritization after a genome-wide association study: an application to nicotine dependence. Bioinformatics 24:1805-11
Bierut, Laura Jean; Madden, Pamela A F; Breslau, Naomi et al. (2007) Novel genes identified in a high-density genome wide association study for nicotine dependence. Hum Mol Genet 16:24-35

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