Modifying quality and equity of care: emerging roles of genetic disease modifiers in β-hemoglobinopathies

Abstract: Genetic disease modifiers (GDMs) strongly affect disease and therapy outcomes, rendering their characterization essential for prognosis, treatment decisions, and therapy development. A paradigm for the importance of GDMs are β-hemoglobinopathies, for which a growing pipeline of emerging curative and disease-modifying therapies are based on the manipulation of GDMs. However, beyond their role as therapeutic targets, GDMs are also gaining clinical importance in the choice and planning of disease-modifying therapies, the selection and customization of curative therapies, and the equitable provision and global reach of therapies across ethnic groups and geo-economic divides. Here, we define roles of GDMs in all 4 of these fields, highlight their potential to promote choice, effectiveness, affordability, and equitable provision of treatment, and emphasize the importance of capacity building through multiethnic GDM-related research. We conclude that consideration of GDMs at all stages of development and care will be critical to addressing the needs of affected communities.