During this year, we reported genome wide association for smoking cessation success in data from an additional clinical trial, with AUROC for a predictive smoking quit success score of 0.64. Smoking quit success genes identified in this fashion include genes that we have identified in studies of addiction vulnerability. A sizable number of these genes have products that are involved in cell adhesion molecule actions. Several are likely to be involved in learning and memory mechanisms. Several are implicated in indivdual differences in regional brain volumes. During this year, we published a novel synthesis of animal models for smoking cessatin focused on mouse models. We have applied many of these tests to an animal model for one of the genes implicated from human studies, CDH13. Extinction/reinstatement of cocaine conditioned place preferences display trends toward difference in CDH13 KO mice;we are currently working with nicotine CPP in these animals. During this year, we reported work that links, for the first time, individual differences in abilities to quit smoking with individual differences in uptake of use of addictive substances, including cigarettes. During this year, we have also followed up on data that identified nominally-significant associations between TRPA1 haplotypes and success in smoking cessation in European Americans. The modest numbers of African American individuals who prefer non mentholated cigarettes disproportionately display TRPA1 alleles that are likely to derive from individuals with European ancestries, at least in 5'aspects of the gene. Chromosomes with apparent recombination at this locus are also identified among African-American smokers who prefer nonmentholated cigarettes.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$88,025
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
Musci, Rashelle J; Bradshaw, Catherine P; Maher, Brion et al. (2014) Erratum to: Reducing Aggression and Impulsivity Through School-Based Prevention Programs: A Gene by Intervention Interaction. Prev Sci :
Uhl, George R; Drgonova, Jana (2014) Cell adhesion molecules: druggable targets for modulating the connectome and brain disorders? Neuropsychopharmacology 39:235
Uhl, George R; Drgonova, Jana; Hall, F Scott (2014) Curious cases: Altered dose-response relationships in addiction genetics. Pharmacol Ther 141:335-46
Uchiumi, Osamu; Kasahara, Yoshiyuki; Fukui, Asami et al. (2013) Serotonergic involvement in the amelioration of behavioral abnormalities in dopamine transporter knockout mice by nicotine. Neuropharmacology 64:348-56
Uhl, George R; Drgon, Tomas; Li, Chuan-Yun et al. (2009) Smoking and smoking cessation in disadvantaged women: assessing genetic contributions. Drug Alcohol Depend 104 Suppl 1:S58-63
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
Drgon, Tomas; Montoya, Ivan; Johnson, Catherine et al. (2009) Genome-wide association for nicotine dependence and smoking cessation success in NIH research volunteers. Mol Med 15:21-7
Uhl, G R; Drgon, T; Johnson, C et al. (2009) Nicotine abstinence genotyping: assessing the impact on smoking cessation clinical trials. Pharmacogenomics J 9:111-5
Uhl, George R (2009) Promise of pharmacogenomics in smoking cessation. Pharmacogenomics 10:1123-5
Drgon, Tomas; Johnson, Catherine; Walther, Donna et al. (2009) Genome-wide association for smoking cessation success: participants in a trial with adjunctive denicotinized cigarettes. Mol Med 15:268-74

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