Twin studies offer a way around this problem. We can estimate the strength of this relationship in twin data because the co-twin data provide a proxy form of information about the relationship between substance use initiation and SUD, by comparing the rates of SUD in the co-twins of those who do versus those who do not initiate. To model this, each variable has its own genetic and environmental risk factors that are specific to either substance use initiation or progression to SUD. All covariance between these two variables is assumed to arise through a regression path. This contingent causal common pathway (CCC) model has a number of extensions, including the multivariate case and more than two-stage phenomena26. The key is the use of twins to overcome the problem of the systematically missing data of not knowing the risk for SUD of individuals who never initiated.
