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 ClinVar. Both variants were well imputed with R2 ranging from 0.831 to 0.994 and 0.862 to 0.999 in the contributing AA and Hispanic/Latino cohorts, respectively (Table 3). Due to the low allele frequency of these variants in AAs and Hispanics/Latinos and even lower frequency in individuals of European descent, both variants were imputed with lower quality using other reference panels (S13 and S14 Tables): the missense variant HBB rs33930165 had R2 as low as 0.127 and 0.456 using 1000G and HRC, respectively, as references; the HBB stop-gain variant rs11549407 was not available in the 1000G reference panel and had R2 as low as 0.413 using HRC as the reference panel. Carrying the 1000G and HRC imputed genotypes forward to association analyses with hematological traits in the subset of our target imputation cohorts where the variants were well imputed (R2 > 0.8), we observed none of the p-values exceeded genome-wide significance threshold. This explains why these variants were not detectable at
