In addition to enabling detailed analysis of TOPMed sequenced samples, TOPMed can enhance the analysis of any genotyped samples72. To this end, we constructed a TOPMed-based imputation reference panel that now includes 97,256 individuals (Extended Data Table 3), including 308,107,085 SNVs and indels (Supplementary Table 15). This is, to our knowledge, the first imputation reference panel that is based exclusively on deep WGS data in diverse samples and greatly exceeds previously published alternatives7,8. For example, the average imputation quality r2 for variants with a frequency of 0.001 in genomes of individuals with an African ancestry increased from around 0.17 in previous panels to 0.96 (Supplementary Fig. 37). Similar improvements were observable in all ancestries that we considered except in South Asian individuals. The minimum allele frequency at which variants could be well-imputed (r2 > 0.3) decreased to around 0.002–0.003% (European or African ancestry in TOPMed). This means that 89% of the approximately 80,000 rare variants with MAF < 0.5% in an average genome of African ancestry can be recovered through genotype imputation using the TOPMed panel.
