that leads to hypo-functionality of (α4β2)2α5 nAChRs (Bierut et al, 2008; Kuryatov et al., 2011; Tammimäki et al, 2012). However, rs16969968:G>A has a low minor allele frequency (MAF) in populations other than those of European descent (Bierut et al., 2008) and the linkage disequilibrium block that includes this SNP extends upstream and downstream of the CHRNA5 gene itself (Saccone et al, 2010). We hypothesized that African-American heavy smokers might have different common (MAF>1%) or rare (MAF<1%) variants in CHRNA5 that would associate with the nicotine addiction phenotype, as does rs16969968:G>A in Europeans.