While theoretically important, the disinhibitory hypothesis in no way excludes other mechanisms of addiction. For example, some individuals self-medicate with alcohol in response to emotional disturbance (Sareen, Bolton, Cox, & Clara, 2006). Individual variation exists in the structure and function of neurotransmitter systems integral to substance use and addiction, such as dopamine, serotonin, and GABA. In cigarette smoking, thanks to large-scale consortia, there are verified genetic influences on biological systems that influence the number of cigarettes smoked per day (Thorgeirsson, et al., 2010). The meta-analysis used to guide SNP selection in the present study was conducted on a discovery sample of 31,266 smokers from the ENGAGE consortium with replication in 45,691 smokers from the Glaxo Smith Kline (Ox-GSK) and Tobacco and Genetics (TAG) consortia. While many SNPs approached genome-wide significance, and are reported in supplementary materials, the authors report three genome-wide significant hits that include SNPs in genes CYP2A6 and CYP2B6 that encode nicotine-metabolizing enzymes (Ray, Lerman, & Tyndale, 2009) as well as in genes that code for nicotinic acetylcholine receptor subunits (CHRNB3 and CHRNA6).
