Our results continue to support an important role for the nonsynonymous CHRNA5 SNP rs16969968 in determining vulnerability to nicotine dependence, as first reported in (Saccone et al., 2007a), and separate in vitro evidence indicates that rs16969968 may indeed be the functional variant explaining the association across the other correlated members of this LD bin (Bierut et al., In press). Due to the extensive LD encompassing not only the CHRNA5-CHRNA3-CHRNB4 cluster but also the neighboring genes LOC123688, PSMA4 and IREB2 (Figures 2A, 3A and S2), further work to definitively identify a causal variant from among all SNPs correlated with rs16969968 will be important.
