Understanding addiction vulnerability genes

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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