Recent studies indicate that individuals with sickle cell disease (SCD) are susceptible to the development of somatic clonal hematopoiesis (CH) mutations, which may predispose to multi- organ failure in early adulthood. We will analyze a multi-center SCD cohort to determine the prevalence of CH mutations and their association with the development of heart, lung or kidney disease, which increase the probability of premature death. By defining the genetic profiles that impact the severity of SCD, we aim to design individualized therapies to safely and prospectively inhibit the development of life-threatening organ damage.