in the reference panel, and even higher, as expected, with higher MAC variants within the JHS sample (S4 and S5 Tables). Similar observations hold true for HCHS/SOL, with slightly lower imputation quality (S6 and S7 Tables). Compared to JHS African Americans, the lower imputation quality in HCHS/SOL Hispanic/Latino individuals is likely attributable to multiple reasons, including (1) the more complex LD structure among Hispanic/Latino individuals due to the admixture of three ancestral populations; (2) the availability of a much smaller subset of rare variants for quality evaluation through MEGA array genotyping in HCHS/SOL (in contrast to the availability of nearly all segregating variants in JHS through high-coverage sequencing); and (3) the smaller number of relevant haplotypes in the TOPMed freeze 5b reference (~26% self-identified AAs compared to ~10% self-identified Hispanics/Latinos). Imputation quality for rare and low-frequency variants that are estimated to be well imputed in Table 1 is further stratified by regional background in HCHS/SOL and displayed in S8 Table. We note that greater numbers of AA and Hispanic/Latino individuals will be included in future releases of sequencing datasets from TOPMed, which we anticipate will further improve imputation quality; inclusion of JHS itself in imputation for other AA cohorts would
