A new generation of interdisciplinary research seeks to use common functional genetic polymorphisms to model emergent variability in brain chemistry that regulates behaviorally relevant brain structure and function. This genetically mediated variability is then being mapped onto trajectories of risk for psychopathology, especially that precipitated by environmental adversity. This Perspective highlights a recent paper in Science that provides a powerful example of how a common functional genetic polymorphism can serve as a translational bridge between human and mouse research, extending our understanding of biological pathways that mediate individual differences in behavior and in risk for psychopathology.