Individual differences in drug abuse vulnerabilities among humans display genetic as well as environmental components. During this year, these investigators continued to explore roles of allelic variants at gene loci in contributing to human individual differences in drug abuse vulnerability and in individual differences in related phenotypes. We reported that individual differences in rate at which use of addictive substances is taken up during adolescence could be indentified for alcohol, tobacco smoking and cannabis smoking using a latent class approach. Individual differences in probabilities of membership of these classes were strongly associated with individual differences in a quit success genotype score, linking (for the first time) genetic influences on uptake of addictive substance use with those on abilities to quit (smoking, at least) . Subsequent to publication of this data, we were ale to identify trajectories for uptake of use of tobacco and cannabis smoking that also display influences of the "quit success" v1.0 genotype score, though no such association was noted for uptake of alcohol use. Several chromosomal regions previously nominnated by our studies have been replicated in datasets from other laboratories that became available during this year. Fine mapping studies have identified particular haplotypes at several gene loci that represent the strongest candidates for addiction vulnerability genes in humans. These studies point toward a role for individual differences in brain structures, as well as functions, in vulnerability to addictions and especial roles for genes encoding molecules that participate in cell adhesion mechanisms. These human data for the most strongly supported genes are now supported by results from studies in mouse models (see other annual reports)

Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2013
Total Cost
$176,051
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
Hall, F Scott; Drgonova, Jana; Jain, Siddharth et al. (2013) Implications of genome wide association studies for addiction: Are our a priori assumptions all wrong? Pharmacol Ther :
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Liu, Q-R; Pan, C-H; Hishimoto, A et al. (2009) Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression and regulation by cannabinoid receptor ligands. Genes Brain Behav :
Li, Chuan-Yun; Liu, Qing-Rong; Zhang, Ping-Wu et al. (2009) OKCAM: an ontology-based, human-centered knowledgebase for cell adhesion molecules. Nucleic Acids Res 37:D251-60
Johnson, Catherine; Drgon, Tomas; McMahon, Francis J et al. (2009) Convergent genome wide association results for bipolar disorder and substance dependence. Am J Med Genet B Neuropsychiatr Genet 150B:182-90
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, George R; Drgon, Tomas; Johnson, Catherine et al. (2009) Addiction genetics and pleiotropic effects of common haplotypes that make polygenic contributions to vulnerability to substance dependence. J Neurogenet 23:272-82

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