The reported findings have important implications for molecular genetic studies of nicotine dependence, but there are limitations that should be noted. For example, the UCSF Family sample was originally selected for alcohol dependence. Thus, it is not clear how the reported findings will generalize to populations without this bias, though a previous study reporting evidence of linkage to the chromosome 2 region used a sample selected for nicotine rather than alcohol dependence (Loukola et al., 2008). Additionally, categorizing ‘never smokers’ and ‘not nicotine dependent’ participants as unaffected individuals may have influenced study results (Munafo et al., 2004). Given that unique genetic influences contribute to the initiation and persistent use of tobacco (Madden & Heath, 1995), combining these participants into a single unaffected category likely limited our ability to detect these unique genetic influences. Nonetheless, there is substantial overlap in the genetic influences contributing to these stages of tobacco use (Sullivan and Kendler, 1999), providing justification for this approach. The statistical power of the present study is another possible limitation. Linkage studies lack sufficient statistical power for identifying loci with small
