Addiction vulnerability genes include those that are likely to harbor allelic variants that contribute to human individual differences in vulnerability to addictions. During this and prior years, we identified dozens of candidates to play such roles based on the covergences between nominally-positive data derived from up to fourteen separate abuser/control or quit success comparisons. During the current year we have reported increasing support from outside samples/datasets for the genes that we have identified most consistently in our own data. We added to evidence supporting roles for many of these genes with novel data concerning rate of "uptake" of developmental use of addictive substances. Genes identified in this fashion include a disproportionate number of genes whose products are involved in cell adhesion molecule actions. During this year we identified additional functional variation at two loci that contain these genes, focusing on extended haplotypes that alters level of expression for CDH13 and PTPRD. These data provide the basis for animal models that replicate, findings in humans and predict stimulant dose-response relationship effects that were recently reported in humans at these two loci. During this year, we reported association between a specific addiction vulnerability phenotype, preference for mentholated cigarettes, and haplotypes in the TRPA1 channel that serves as a menthol receptor in the few African American subjects who prefere nonmentholated cigarettes. D

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National Institute on Drug Abuse
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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
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 :
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
Ishiguro, Hiroki; Gong, Jian-Ping; Hall, F Scott et al. (2008) Association of PTPRB gene polymorphism with drug addiction. Am J Med Genet B Neuropsychiatr Genet 147B:1167-72
Han, Joan C; Liu, Qing-Rong; Jones, MaryPat et al. (2008) Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med 359:918-27
Onaivi, Emmanuel S; Ishiguro, Hiroki; Gong, Jian-Ping et al. (2008) Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. PLoS ONE 3:e1640