We have replicated across different countries, cultures and ascertainment methods the key observation from multivariate twin analyses that a substantial majority of the genetic risk for DA is shared across different substance classes. This provides, we suggest, convincing evidence that genetic variation in the genes that code for the primary sites of action of the psychoactive drugs themselves play a minor role in human individual differences in risk for DA. Instead, these consistent set of findings suggest that the genetic variants that influence human DA are likely to include psychological traits and/or brain systems which impact responses to a diversity of substance classes. These likely include personality and personality-like traits that impact on risk for experimentation with most psychoactive compounds (Krueger et al., 2002; Zuckerman, 1972), frontal inhibitory systems that modulate impulsive reward-related behaviors (Dick et al., 2010; Koob and LeMoal, 2006), and brain systems that subserve the hedonic response to a most substances of abuse (Koob and LeMoal, 2006).
