The current observations contain significant limitations that should be considered in their interpretation. First, the modest sizes of the samples used for these studies provide moderate power, at best, to detect gene variants related to nicotine dependence and successful quitting. As noted in the power calculations, the number of false negative results is likely to be higher for allelic variants that produce small effects. Second, in conjunction with the modest sample sizes, we have also imposed stringent requirements for the genes listed in Table 1. Each of these genes is required to contain SNPs that display nominally significant abuser/control allele frequency differences in four prior samples, and also to display enhanced Monte Carlo p values when the current dataset is added to previously-obtained datasets. While these analyses reduce the probability that these genes will represent false positives, it is also likely to lead to many false-negative results. If we even allow genes whose Monte Carlo probabilities are not reduced by adding the current data to be included, most of the genes previously supported by the four prior datasets for other addictions [22,31,49] would also be included in Table 1 (data not shown).
