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Both linkage studies and genome wide association studies (GWAS) have identified candidate genes/genomic regions associated with nicotine dependence ( Genetic factors significantly influence both smoking initiation and persistence, a schematic of these influences are presented in Figure 1, these include genes associated with differences in nicotine's metabolic capacity and nicotine effects on central nervous system neurotransmitter functionality, specifically the dose that modulate direct and indirect effects on nAChR, dopaminergic and opioidergic activity, respectively