Response to varenicline treatment is associated here with polymorphisms in multiple loci encoding nicotinic receptor subunits. Chief among these are the CHRNA4 and CHRNB2 loci, encoding the α4 and β2 nicotinic receptor subunits. Receptors comprised of these subunits are the specific targets of varenicline's activity, thus it is perhaps not surprising that these loci would be associated with varenicline response. In addition to these loci, there is also an association to varenicline response with polymorphisms in the chr15q25 locus. This, too, is consistent with varenicline activity, particularly given recent evidence demonstrating the importance of α5 subunits in predominantly α4β2 nicotinic receptors and the emergence of risk alleles in this locus as a primary factor in nicotine dependence (Fowler et al, 2011; Kuryatov et al, 2011; Zheng et al, 2011). An association between the 15q25 locus and response to varenicline also supports an argument that response to varenicline is related to nicotine dependence itself. Due to the high degree of LD among loci in this region, it is difficult to discriminate causative loci. The positive markers for varenicline response are in
