To summarize, there were two main findings of this study. First, in two large samples, we verified the association of rs16969968 and rs1051730 with nicotine dependence when FTND scores were used as phenotype. Of these two SNPs, rs16969968 is a non-synonymous polymorphism, changing Asp to Asn at the 398th amino acid position of the CHRNA5 gene. This provides an opportunity to directly test this polymorphism in animal models. Combining these results with those obtained from prior studies [Saccone et al., [2007]; Berrettini et al., [2008]; Bierut et al., [2008]; Thorgeirsson et al., [2008]], we believe that the α5 and α3 genes are established as one of the best replicated genes imposing risks to tobacco smoking and nicotine dependence. Functional studies of these genes in animal and cellular models should follow. Second, we also found significant association with SymAlcAD for the same markers associated with FTND scores. However, the effects were in the opposite direction. While this finding was in agreement with others' reports [Grucza et al., [2008]; Wang et al., [2008]], it is inconsistent with the findings of epidemiological studies.
