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

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2013
Total Cost
$176,051
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
Zhong, Xiaoming; Drgonova, Jana; Li, Chuan-Yun et al. (2015) Human cell adhesion molecules: annotated functional subtypes and overrepresentation of addiction-associated genes. Ann N Y Acad Sci 1349:83-95
Uhl, George R; Drgonova, Jana; Hall, F Scott (2014) Curious cases: Altered dose-response relationships in addiction genetics. Pharmacol Ther 141:335-46
Ishiguro, Hiroki; Hall, Frank S; Horiuchi, Yasue et al. (2014) NrCAM-regulating neural systems and addiction-related behaviors. Addict Biol 19:343-53
Uhl, George R; Drgonova, Jana (2014) Cell adhesion molecules: druggable targets for modulating the connectome and brain disorders? Neuropsychopharmacology 39:235
Uhl, G R; Walther, D; Musci, R et al. (2014) Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances. Mol Psychiatry 19:50-4
Bruehl, Stephen; Apkarian, A Vania; Ballantyne, Jane C et al. (2013) Personalized medicine and opioid analgesic prescribing for chronic pain: opportunities and challenges. J Pain 14:103-13
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 :
Bough, K J; Lerman, C; Rose, J E et al. (2013) Biomarkers for smoking cessation. Clin Pharmacol Ther 93:526-38
Munafò, Marcus R; Timofeeva, Maria N; Morris, Richard W et al. (2012) Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure. J Natl Cancer Inst 104:740-8

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