AbstractThe stress that accompanies caring for one’s parent, and the contribution of that stress to adverse physical and mental-health outcomes, is extensively studied and widely acknowledged. Yet there has been almost no attempt to incorporate the well-documented role of genetic variation in psychological distress into research on caregiving. We use phenotypic data from a large, population-based sample linked to extensive genotype data to develop a polygenic risk score (PRS) for depression, and test for both direct and interactive effects of the PRS in a multilevel repeat-measures model of caregiver-related stress. We distinguish three groups: potential caregivers (those with a living parent who does not need care), noncaregivers (those who do not provide care to their parent that needs care), and caregivers. We also obtain separate estimates according to the gender of both the parent and child. We found that a parent’s need for care, and the child’s provision of care, are associated with depression in some but not all cases; in contrast the PRS was significantly associated with the risk for increased depressive symptoms (with P ≤ 0.01) in all cases. These findings support an additive genetic contribution to the diathesis-stress model of depression in the context of caregiving.