Our ancestry-stratified imputation-based discovery meta-analysis revealed two blood cell trait associations that have not been previously reported, at a genome-wide significant threshold of p<5×10−9 in Hispanics/Latinos and p<1x10-9 in AA populations, based on appropriate significance thresholds for whole genome sequencing analysis [31]. One signal was revealed in each ancestry group: hemoglobin subunit beta (HBB) missense (p.Glu7Lys) variant rs33930165 (gb38:11:5227003:C:T) associated with increased WBC in AAs (β = 0.35 and p = 8.8x10-15, adjusting for SNP rs2814778 and removing potential minor allele homozygotes) (Table 3), and HBB stop-gain (p.Gln40Ter) variant rs11549407 (gb38:11:5226774:G:A) associated with lower HGB and HCT in Hispanics/Latinos (β = -1.92, p = 1.5x10-12; β = -1.66, p = 8.8x10-10). Both variants were either low frequency or rare: the HBB missense variant rs33930165 (hemoglobin C variant) has a MAF of 1.14% among the imputed AA discovery samples and is even rarer in non-AA individuals (absent in Europeans in 1000G); the stop gain variant rs11549407 has a MAF of 0.03% (MAC ~ 15) among the imputed Hispanics/Latinos and is monomorphic among the AAs. Both variants are classified as pathogenic in
