magnitude smaller than HRC. This is especially problematic given the complex LD structure in admixed populations. The NHLBI Trans-Omics for Precision Medicine (TOPMed) Project has recently generated deep-coverage (mean depth 30x) whole genome sequencing (WGS) on more than 50,000 individuals from >26 cohorts and from diverse ancestral backgrounds (notably including ~26% AA and ~10% Hispanic/Latino participants), and now provides an unprecedented opportunity for substantially enhancing imputation quality in under-represented admixed populations and subsequently boosting power for mapping genes and regions underlying complex traits. Here we demonstrate the improvements in rare variant imputation quality in AA and Hispanic/Latino populations using TOPMed as a reference panel versus 1000G and HRC panels, and subsequently identify two low-frequency/rare HBB variant associations with blood cell traits in AA and Hispanic/Latino samples using TOPMed-imputed genotyping array data.
