Study design and datasets. The SGP cohort consists of 722 participants from BCM or the SCCRIP cohort at St. Jude Children’s Research Hospital who were analyzed by WGS. Globin gene analysis was performed for all participants to ascertain α-thalassemia, β-thalassemia, and hereditary persistence of fetal hemoglobin). GWASs and candidate gene–based testing for RBC %HbF were performed for 585 participants with WGS-confirmed HbSS or HbSβ⁰-thalassemia for whom RBC indices and %HbF were available after the age of 2 years and to whom no hydroxyurea therapy had been administered for at least 90 days. Genetic association studies of VOP events were performed for 327 SCCRIP participants who were analyzed longitudinally at ages 1 to 6 years. Covariates for VOP association studies included α-thalassemia status, modifier alleles for HbF expression, and genetic variants associated with pain of various etiologies. Validation for the SCCRIP VOP studies was performed by analyzing SCRIPP data with TSIR and by analyzing VOP-genotype associations in the SAC cohort.