The association of the HBB missense (p.Glu7Lys) variant 11:5227003:C:T or rs33930165 with higher total WBC (β = 0.35, p = 8.8x10-15) among AA was unexpected; rs33930165 has been associated with red blood cell indices such as mean corpuscular hemoglobin concentration [20] but not with white blood cell traits. Because of the higher allele frequency of this variant and also the larger number of AA samples (n = 6,743) in TOPMed freeze 5b, we were able to replicate this HBB rs33930165 association with total WBC in an independent sample (β = 0.27 and p = 4.6x10-4) of AA individuals. By contrast, there was no significant association of the HBB rs33930165 p.Glu7Lys variant with HGB and a modest association with lower HCT in the AA discovery and replication data sets (discovery HCT β = -0.122, p = 0.012; HGB β = 0.110, p = 0.022; replication HCT β = -0.239, p = 0.002; HGB β = -0.009, p = 0.909). The minor allele T of rs33930165 encodes an abnormal form of hemoglobin, Hb C, which in the homozygous state is associated with
