The mixture analyses in this study afforded a detailed analysis of the phenotypes in conjunction with an equally detailed investigation of genetic effects. Nine of the ten investigated SNPs were previously analyzed by Schlaepfer et al. (2008) in two samples that were independent of the current sample, thereby providing ample opportunity to replicate and extend previous findings. In addition, SNP rs16969968 was investigated, which had been replicated in several different studies using various different substance-related phenotypes, and which has been shown to change receptor function (Bierut et al. 2008). Although our results concerning onset of smoking are weak, the main body of results from this study is consistent with previous findings regarding the role of the CHRNA5/B4/A3 gene cluster. The allelic effects reported by Schlaepfer et al. (2008) were in the same direction as the corresponding effects in our analyses. Importantly, our work shows that the importance of this gene cluster is not limited to tobacco and alcohol initiation, but that it extends to the onset of use of various different substances.
