quantity and nicotine dependence and therefore suggested that the link with lung cancer is primarily mediated through the smoking-related phenotypes. However, the other two studies (11, 12) found little or no evidence for the involvement of smoking behavior in the association and concluded that the genetic variation affected lung cancer directly. Thus, while there is considerable evidence for the importance of common variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster, it is not clear which phenotypes are directly associated with these SNPs.
