Addiction vulnerability genes include those that are likely to harbor allelic variants that contribute to human individual differences in vulnerability to addictions. During 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. Genes identified in this fashion include a disproportionate number of genes whose products are involved in cell adhesion molecule actions. During this year we increased the accuracy of these designations by reannotating a list of cell adhesion molecules, designating those that were more involved in structural vs informational roles, and identifying those as more informational as more overrepresented in the list of addiction-vulnerability genes identified in prior years. We have developed additional functional variation at three loci that contain these genes, focusing on extended haplotypes that alter level of expression for CDH13, PTPRD and CSMD1 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 three loci. These data provide the basis for validation of murine models for at least some of the common allelic variation at these three loci at which genes encode addiction-associated cell adhesion molecules. Publications Generated during the 2015 Reporting Period

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10
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2015
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National Institute on Drug Abuse
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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
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, George R; Drgonova, Jana; Hall, F Scott (2014) Curious cases: Altered dose-response relationships in addiction genetics. Pharmacol Ther 141:335-46
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
Bough, K J; Lerman, C; Rose, J E et al. (2013) Biomarkers for smoking cessation. Clin Pharmacol Ther 93:526-38
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 140:267-79
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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