Sickle cell disease (SCD) is a Mendelian disorder characterized by a point mutation in the β-globin gene that leads to sickling of erythrocytes. Several studies have shown that absolute neutrophil count is strongly associated with clinical severity of SCD, suggesting an apparent role of white blood cells (WBC). However, the mechanism by which genetic variants lead to leukocyte difference in SCD patients remains unclear.

Genome wide association (GWA) analyses were carried out with 2409 participants. Association of WBC count and genetic markers were investigated in homozygous sickle cell anemia (HbSS) participants and compound heterozygous sickle cell hemoglobin C (HbSC) participants.

GWA analyses showed that variants in genes TERT, ACKR1 and FAM3C were associated with WBC count variation.

The well-studied association between WBC count and Duffy null phenotype (variant in ACKR1) in healthy populations was replicated, reinforcing the influence of the SNP rs2814778 in WBC.

Genetics plays an important role in regulating WBC count in patients with SCD. Due to the relationship between reduced WBC count and elevated clinical presentation, our results points to potential therapeutic targets for patients with SCD.