The current study aimed to identify genetic effects on the vulnerability to substance dependence. We hypothesized that common genetic variants account for at least one-half of the genetic variance observed in twin/adoption studies. Furthermore, to demonstrate the validity of these findings we utilized three DSM-IV based definitions of comorbid drug dependence and further hypothesized that a common set of genetic factors would account for any and all genetic variance identified across the definitions. To test these hypotheses we first used factor analysis to replicate prior work (21) and determine the existence of a common factor indicated by either drug dependence diagnosis (DD; i.e., 3+ DSM-IV criteria in a 12-month period) or problem use (PU; i.e., 1+ DSM-IV criteria (lifetime)). Second, we examined genome-wide additive genetic influences on the observed factors, as well as the summary measure, dependence vulnerability (DV). Clinical definitions (DD), sub-clinical thresholds (PU), and the DV summary score were analyzed separately to explore how the measurement approach used to reflect substance-related problems affects the magnitude of identified additive genetic effects. Finally, we used a bivariate GCTA model to test whether DD, PU and DV index the same genetic liability.
