In our meta-analysis of African-Americans, rs16969968 is more strongly associated with heavy smoking (OR=1.62, 95%C.I.=1.21–2.17, p=0.0011, N=1807) than rs1051730 (OR=1.15, 95%C.I.=1.03–1.28, p=0.011, N=7352). SNP rs16969968 is the most strongly associated polymorphism across all three populations and the only variant meeting the consistent association threshold in our study. In addition, SNP rs16969968 causes an amino acid change in the nicotinic receptor α5 subunit and alters function of its receptor [Bierut, et al. 2008]. The observed consistent associations across diverse populations, combined with the results of biological experiments on rs169669968, provide converging evidence that rs16969968, rather than rs1051730, is most likely one causative variant in this region driving the strongest association signal.
