Genetics and Genomics in Sickle Cell Disease in Africa

Advanced genomic technologies are revolutionizing our ability to understand complex diseases. Large-scale population studies are needed to realize the potential of using individual genetic information to personalize treatments for better patient outcomes for chronic non-communicable diseases, such as sickle cell disease (SCD). SCD is recognized as a benchmark genetic disorder for study both in Africa and globally due to its unmet health burden and the potential utilization of genomic knowledge for improving the health outcomes for individuals living with the disease. Over the past two decades, groundbreaking genomic research in SCD has led to the discovery, fine mapping, and validation of genetic and epigenetic variants of importance for SCD. These include variants in genes such as BCL11A, HBG, MYB, KLF1, and FLT1, which are all associated with fetal hemoglobin expression, a major modifier of disease severity in SCD. There has also been increased genomic knowledge of other SCD modifiers, including the distribution of alpha- and beta-thalassemia variants in Africa, and infectious disease related markers such as APOL1. Pioneering pharmacogenomics studies for hydroxyurea are promising and have unveiled the importance of the implementation of such studies for all SCD therapeutics, including small molecules and recent gene-based therapies. Genomic research for the development of personalized medicine for SCD must involve countries in Africa due to the high prevalence of the disease in these countries, the high African genetic diversity that influences disease progression, and the potential to follow treatment outcomes in large cohorts of patients. These findings hold great promise to lead to a better understanding of SCD biology and treatment responses, the discovery of new therapies, and informing the design and execution of much needed clinical trials.