Abstract

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 more than 100 such genes based on the covergences between nominally-positive data derived from up to ten separate abuser/control comparisons. We added to evidence supporting roles for many of these genes with additional data from several comparisons between nicotine depdendent and control samples and substance dependent and control samples with higher marker densities. We added additional support from comparisons between smokers who were successful vs unsuccessful in quitting in clinical trials and in community samples. 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 the frequent functional variations at a locus that contain these genes, focusing on a splicing variant.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADA000492-04
Application #
7966853
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2009
Total Cost
$301,817
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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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