Primary and secondary modifiers of the β thalassemia phenotype. They include variable output from the β globin (β genotype); variable output from the α globin genes (α genotype) and variable Hb F response (co-inheritance of different QTLs controlling Hb F and F cell levels).

The consequences of these factors is the degree of chain imbalance (α/non-α globin ratio) and severity of ineffective erythropoiesis.