The results of the nicotine-dependence vs control comparisons from the current study provide substantial confirmation for a number of genes in several gene classes that have been nominated and confirmed in prior addict vs control studies. Seven previously nominated genes related to cell adhesion processes, CNTN6, LRRN1, SEMA3C, CSMD1, PTPRD, LRRN6C and CDH13 each receive additional support from 100,000 Monte Carlo simulation trials. The convergence between current and previously-obtained data suggest that allelic variants in these genes are thus likely to contribute to individual differences in vulnerability to a variety of addictive substances (Table 1). Four genes related to enzymatic activity, SIPA1L2, PDE1C, PDE4D and PRKG1 each receive similar support. Genes involved in protein processing, a transcriptional regulator, and genes involved in channel, transporter, structural, disease and other processes receive similar support. Three G-protein coupled receptors, the GRM7 metabotropic glutamate receptor, the orphan GPR154 and the HRH4 histamine receptor also receive such support. Each of these genes, taken individually, is thus supported by data from studies of individuals selected on the basis of their dependence on illegal substances (largely cannabis, stimulants and opiates), methamphetamine, alcohol and tobacco.
