genotype causes smoking, but it also causes the environment of nicotine intake. Some have theorized that environmental exposure to drugs and alcohol acts as a “gateway,” in which the experience of drug effects cause further use of other, possibly “harder” drugs (e.g., see (Kandel & Jessor, 2002)). The present study tests whether these known nicotine SNPs are related also to alcohol use. A positive association would tend to support a gateway-type effect of nicotine exposure on alcohol use, especially if a more generalized risk etiology (e.g., disinhibition) can be ruled out. At first blush the method appears paradoxical in that genetic variants, here SNPs, are actually used as proxies for environmental exposure. This approach is called Mendelian randomization (Smith & Ebrahim, 2003, 2005), and has been successfully applied to address environmental effects on metabolic syndrome (Timpson, et al., 2005), drug use (Irons, Iacono, Oetting, & McGue, 2012; Irons, McGue, Iacono, & Oetting, 2007), and other diseases (Schatzkin, et al., 2009).
