Reports in the literature support this idea that comparing exposed, regular users may be one way to tease out genes which contribute to dependence. For example, in the recent studies by Bierut et al (2007) and Saccone et al (2007) who used a minimum of smoking 100 or more times, they found highly significant associations with CHRNB3 SNPs and nicotine dependence (Bierut et al, 2007; Saccone et al, 2007). However, other studies that used more inclusive criteria did not find results that were as significant (Greenbaum et al, 2006). Replication of associations between specific SNPs and complex traits has been a challenge for researchers investigating and interpreting these studies. While lack of replication may be due to the initial finding being a false positive, there are many other sources of inconsistency between findings, including the definition of the phenotype as well as inclusion criteria of the sample. However, it is important to keep in mind that using highly stringent inclusion criteria can greatly reduce power due to reduced sample size and phenotypic heterogeneity. For this reason, we conducted a secondary
