The saturated model used in these analyses is depicted in Fig. 1. This is a modification of the CCC model (Kendler et al. 1999), and takes into consideration the contingency of ND on regular tobacco use. Thus, liability to dependence is a function of both risk shared with regular tobacco use (depicted by the β pathway in Fig. 1) and risk factors independent of regular tobacco use. If all liability to dependence can be accounted for by liability to regular use, the β common pathway coefficient will approach 1, and the path coefficients a3,3, c3,3 and e3,3 will approach 0. Our model also includes MD, which is not contingent on regular tobacco use or ND, and allows for shared genetic and environmental liability between MD and both tobacco-related variables. This model allows us to assess quantitative sex effects by obtaining parameter estimates for both sexes and testing whether these parameters can be constrained to equality without a loss in model fit. Because of the complex model design, we opted not to test for qualitative sex effects (wherein the same trait
