Genetic Modifiers of Sickle Cell Disease.

Sickle cell disease (SCD) is characterized by tremendous phenotypic heterogeneity across patients, but this clinical variability is poorly understood, thus motivating the search for genetic modifiers. The early identification of genetic variants that control fetal hemoglobin levels-a strong modifier of severity in SCD-served as a powerful example in support of these genetic experiments. Although there have been successful discoveries (eg, UGT1A, APOL1), many of the reported genetic associations remain controversial. The emergence of large-scale SCD cohorts and their integration into genetic and other omic-type research programs should bring SCD patients closer to the promises of precision medicine.