The statistically significant, dominant association between HBB rare variants and hemoglobinopathies and the high PPV (0.55, Table 3) found in our cohorts are driven by a mixture of some individuals who may have β-thalassemia intermedia, a less severe form of the disease that is sometimes inherited in a dominant fashion, and many individuals with β-thalassemia minor, who are generally asymptomatic but often have mild anemia [28, 29]. Here, HBB is linked to anemia (phenotype).