D'Onofrio and colleagues (2003) demonstrated that the offspring of twins design can address limitations of the classical twin design and can be used to quantify processes underlying intergenerational transmission of disease. The classic twin design may overestimate the variance due to genes because gene x shared environment interactions are attributed to additive genetic variance unless specifically modeled (Heath and Nelson, 2002; Jacob et al., 2001). If there is not a main effect of the shared environment, it may appear that family resemblance is completely determined by genetic transmission. Also, in the case when a main effect of the shared environment is masked by genetic dominance (non-additive genetic factors) it may appear that family resemblance is determined only by genetic transmission.
