Encouraged by these substantial gains in information content for low-frequency and rare variants, we proceeded with imputation in several additional AA and Hispanic/Latino data sets with array-based genotyping (S1 and S9 Tables), followed by association analyses with quantitative blood cell traits to evaluate the power of TOPMed freeze 5b-based imputation in minorities for discovery of genetic variants underlying complex human traits. We specifically chose hematological traits for several reasons. First, these traits are important intermediate clinical phenotypes for a variety of cardiovascular, hematologic, oncologic, immunologic, and infectious diseases [11]. Second, these traits have family-based heritability estimates in the range of 40–65% [12, 13], and have been highly fruitful for gene-mapping with >2,700 common and rare variants identified, though primarily in individuals of European ancestry [14–19]. Third, these traits remain under-studied in admixed AA and Hispanic/Latino populations, despite evidence for the existence of variants with distinct genetic architecture in AAs and Hispanics/Latinos [20–22]. For example, while hundreds of variants identified in genome-wide association studies (GWAS) of WBC in individuals of European descent explain only ~7% of array heritability, the African specific
