This document reports on a study that identified variants in the FOXO3 gene associated with higher fetal hemoglobin (HbF) levels in patients with sickle cell anemia. The study used whole exome sequencing on 1000 pediatric sickle cell patients and identified 7 FOXO3 variants linked to reduced HbF. Knockdown and overexpression experiments in cell lines and primary erythroid cells demonstrated that FOXO3 regulates g-globin expression. Further studies are planned to validate the associations in more patients, determine the mechanisms of FOXO3 regulation of g-globin, and identify potential drug targets in the pathway to induce HbF.