This funding opportunity announcement (FOA) issued by National Heart, Lung, and Blood Institute (NHLBI) invites applications to conduct functional analyses of identified genetic variations related to heart, lung, blood and sleep phenotypes, using amenable in vitro or animal model systems. Exploratory/Developmental Phased Innovation (R21/R33) grant applications should identify and justify the genetic variants that they propose to test for functionality, the phenotype(s) the variants are associated with, and the functional measures that will be used to validate them. This FOA provides support for two years (R21 phase) for research planning activities and feasibility studies, followed by possible transition of up to three years of expanded research support (R33 phase). The total project period for an application submitted in response to this FOA may not exceed five years. This FOA requires measurable R21 milestones.