NEUROBIOLOGY AND GENETICS OF PANIC, TS, AND OCD. This is an application for an NIMH K02 (Independent Scientist) award. The goal of the proposal is to continue specialized training for the PI, a psychiatrist, in molecular and population genetics.
The aims of the research are to (a) locate genes affecting risk for panic disorder by genetic linkage; (b) identify genes influencing risk for Tourette's syndrome and obsessive-compulsive disorder using the haplotype relative risk (HRR) family association method; (c) identify genes associated with specific phenotypes (recognized, eg, by imaging studies) within groups affected with illness using association methods; and (d) identify specific mutations associated with phenotype by mutational analysis and sequencing. Under some circumstances, genome scan- directed linkage studies are most useful in identifying genes predisposing to illness; under other circumstances, HRR studies may be more efficient. For very strong candidate gene hypotheses, mutational analysis may be employed directly. Preliminary results have been generated using all of these methods. For our panic disorder linkage project (""""""""a""""""""), we have obtained DNA from 201 individuals in 21 families, as of May 1995. We have used the HRR method to identify a genetic association between Tourette's syndrome and an allele at the D4 dopamine receptor locus ('b""""""""). In the area of genotype/phenotype association, we have reported an association between cocaine-induced paranoia and dopamine transporter alleles; we have obtained preliminary data using SPECT imaging techniques regarding the relationship between alleles at the D2 dopamine receptor locus (DRD2) and brain D2 receptor density (""""""""c"""""""". We propose to complete a genome scan for the panic disorder linkage project; attempt to identify other genes influencing risk for Tourette's syndrome and obsessive-compulsive disorder; and identify other genotype-phenotype relationships using imaging studies as a way to ascertain phenotype directly.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH001387-03
Application #
2883324
Study Section
Epidemiology and Genetics Review Committee (EPI)
Program Officer
Moldin, Steven Owen
Project Start
1996-09-01
Project End
2002-02-28
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Zuo, Lingjun; Gelernter, Joel; Kranzler, Henry R et al. (2010) ADH1A variation predisposes to personality traits and substance dependence. Am J Med Genet B Neuropsychiatr Genet 153B:376-386
Tang, Yi-lang; Kranzler, Henry R; Gelernter, Joel et al. (2009) Transient cocaine-associated behavioral symptoms rated with a new instrument, the scale for assessment of positive symptoms for cocaine-induced psychosis (SAPS-CIP). Am J Addict 18:339-45
Zuo, Lingjun; Luo, Xingguang; Kranzler, Henry R et al. (2009) Association study of DTNBP1 with schizophrenia in a US sample. Psychiatr Genet 19:292-304
Luo, Xingguang; Zuo, Lingjun; Kranzler, Henry et al. (2008) Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations. Am J Med Genet B Neuropsychiatr Genet 147B:1028-39
Luo, Xingguang; Kranzler, Henry R; Zuo, Lingjun et al. (2008) ADH7 variation modulates extraversion and conscientiousness in substance-dependent subjects. Am J Med Genet B Neuropsychiatr Genet 147B:179-86
Luo, Xingguang; Kranzler, Henry R; Zuo, Lingjun et al. (2007) Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans. Hum Mol Genet 16:380-90
Luo, Xingguang; Kranzler, Henry R; Zuo, Lingjun et al. (2007) CHRM2 variation predisposes to personality traits of agreeableness and conscientiousness. Hum Mol Genet 16:1557-68
Luo, Xingguang; Kranzler, Henry R; Zuo, Lingjun et al. (2006) ADH4 gene variation is associated with alcohol dependence and drug dependence in European Americans: results from HWD tests and case-control association studies. Neuropsychopharmacology 31:1085-95
Luo, Xingguang; Kranzler, Henry R; Zuo, Lingjun et al. (2006) Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence. Am J Hum Genet 78:973-87
van Dyck, Christopher H; Malison, Robert T; Jacobsen, Leslie K et al. (2005) Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene. J Nucl Med 46:745-51

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