Abstract

Sickle cell disease (SCD) is a monogenic hematologic disorder that causes significant morbidity and mortality 
worldwide, disproportionately affecting populations of African, Indian, Middle Eastern, and Mediterranean 
ancestry. Whole-exome sequencing (WES) offers a precision public health approach by identifying both primary 
HBB mutations and modifier genes that influence disease severity, clinical complications, and therapeutic response. 
This paper synthesizes the evidence supporting WES for SCD, explores equity considerations in genomics 
implementation, and examines challenges in translating bench discoveries to population-level interventions. Key 
barriers include infrastructural limitations, workforce capacity, regulatory compliance, and the 
underrepresentation of marginalized populations in genomic studies. Case studies from Quebec, Australia, and 
Nordic countries highlight strategies for successful implementation, including integration with public health 
priorities, cross-sector collaboration, and data governance. Future research should focus on understanding genetic 
modifiers across diverse populations, evaluating intervention efficacy, and ensuring equitable access to genomics
informed care. By aligning precision medicine with public health objectives, WES has the potential to reduce 
disease burden, improve health equity, and inform scalable interventions for SCD globally.