© 2017 Hogrefe Publishing. Previous research is mixed regarding the relation between dopamine and Novelty Seeking. The goals of the current study were to support the hypotheses that Novelty Seeking is associated with dopamine genes and that modeling genetic risk score increases the utility of genetic information in hypothesis-driven research. The results showed that higher hypodopaminergic genetic risk score positively predicted higher Novelty Seeking score, F(1, 115) = 5.76, p < .01, R2 = 0.06. The findings support study hypotheses and, in combination with previous studies, show the utility of empirically validated system-based risk scores as a means of modeling genetic predisposition in neurobiological systems. This approach provides a mechanism for incorporating genetic predisposition into theory-driven multivariate etiological models of psychological constructs such as personality and mental illness.