A global view of disparity in imputation resources for conducting genetic studies in diverse populations

Genotype imputation is an essential tool for genome-wide association studies (GWAS), especially when the whole-genome sequencing of the sample is not readily available. By comparing an imputation reference panel consisting of individuals whose genomes were previously sequenced, one can greatly increase the coverage of the genomic dataset to increase the statistical power of the association study. However, previous imputation reference panels consist largely of individuals of European ancestry and are severely deficient in sampling populations from other continents. In May 2020, the Trans-Omics for Precision Medicine (TOPMed) imputation panel became available online with a larger sample size and claimed to obtain better imputation quality for African and Hispanic/Latino American populations since they improved the representation in sequencing data from those populations. However, it remains unclear how effective the TOPMed data serves as an imputation reference for other global populations such as East Asians, Southeast Asians, and Polynesians. We found that the imputation quality of the TOPMed imputation panel for global populations outside of the United States still lags behind that for the European populations. Our assessment thus call for more sequencing studies to be conducted more equitably for populations around the globe so to enrich the representation of our current imputation reference panel and to enable powerful genetic association studies in these global populations.