methods can scale to ~100 million markers in populations containing over thousands of individuals. TOPMed freeze 5b imputation is slightly more computationally intensive than use of the HRC reference panel (and takes nearly eight times longer than 1000G based imputation using the Michigan imputation server). However, we feel this increase in computational time is more than justified by the large number of additional well-imputed variants. We would note that the gains in imputation quality for AA and Hispanic/Latino populations using the TOPMed WGS reference panel likely do not apply to populations poorly represented in TOPMed freeze 5b (such as South Asians); future large-scale sequencing, including in later freezes of TOPMed, will improve imputation quality further across global populations.
