Using a large-scale genetic study of stroke (MEGASTROKE) and a study of endothelial function in adolescents (ALSPAC [Avon Longitudinal Study of Parents and Children]), we identified a genetic locus in the PDE3A gene, encoding phosphodiesterase 3A, that was associated with both endothelial function and ischemic stroke. Here, PDE3A is linked to ischemic stroke.