individuals with beta thalassemia among admixed populations from Central and South America [34, 35], which are geographically and genetically similar to some of the Hispanic/Latino samples included in our imputation-based discovery sample. While the individuals carrying the HBB p.Gln40Ter allele in our unselected population-based Hispanic/Latino sample were all imputed heterozygotes (consistent with “thalassemia minor” and generally considered healthy), there is increasing evidence that silent carriers of beta-thalassemia and sickle cell mutations may be at risk for various health-related conditions [36, 37]. Due to the relatively small number of Hispanic/Latino individuals with blood cell trait data in TOPMed freeze 5b (n~1,080), including only one heterozygote carrier of rs11549407 in those with blood cell traits measured, we were unable to perform a well-powered replication of the association of rs11549407 with HGB and HCT. Moderate anemia is known to occur in some individuals with thalassemia minor, however, concordant with our results [38].
