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 LD (>0.6) with nicotine dependence markers (as well as markers for nausea; see below), thus these associations may be reflecting common functional alleles. In fact, the alleles that are associated with increased odds of quitting with varenicline are in LD with alleles associated with a decreased risk of nicotine dependence. This may be true of bupropion and placebo responders as well, although there are not sufficient subjects in these groups to detect such an effect. The relevance of the association with the CHRNA7 locus is less clear, although varenicline does bind to homopentameric α7 nicotinic receptors (Coe et al, 2005), however with reduced affinity in comparison with α4β2 receptors (Amos et al, 2008; Hung et al, 2008; Thorgeirsson et al, 2008).
