We also found significant association with symptoms of alcohol abuse and dependence in our combined sample, but the associated alleles were the opposite of those associated with the FTND score. While this finding is similar to those reported recently by others [Grucza et al., [2008]; Wang et al., [2008]], it is not consistent with epidemiological studies where nicotine dependence is consistently found to be positively correlated with alcohol abuse and dependence. In analyses without using FTND as covariate, both rs16969968 and rs1051730 was nominally significant (P = 0.018 and 0.029 respectively, data not shown). However, the association became stronger when accounting for the effect of FTND scores. These analyses further support the hypothesis that the effects of FTND and SymAlcAD at these variants are truly in the opposite direction. It is possible that these findings reflect the different actions of the two substances: nicotine is a stimulant whereas alcohol is a depressant. So, for example, if those with Asn alleles are more predisposed to enjoy the action of stimulants, they may be less likely to enjoy the effects of depressants.
