A High-resolution Haplotype-resolved Reference Panel Constructed from the China Kadoorie Biobank Study

Abstract

Precision medicine relies on high-accuracy individual-level genotype data. However, the whole-genome sequencing (WGS) is currently not suitable for studies with very large sample sizes due to budget constraints. It is particularly important to construct highly accurate haplotype reference panel for genotype imputation. In this study, we selected 9,950 individuals from the China Kadoorie Biobank (CKB) cohort and 50 Chinese samples from the 1000 Genome Project (1KGP) for medium-depth WGS to construct a CKB reference panel. The results of imputing microarray datasets showed that the CKB panel outperformed the extended high coverage 1KGP, TOPMed, ChinaMAP, and NuyWa panels in terms of both the number of well-imputed variants and imputation accuracy. In addition, we have completed the imputation of over 100,000 CKB microarray data with the CKB panel, and the after-imputed genotype data is the hitherto largest whole genome data of the Chinese population. Finally, we developed an online server for offering free genotype imputation service based on the CKB reference panel (https://db.cngb.org/imputation/). We believe that the constructed CKB reference panel is of great value for imputing microarray or low-depth genotype data of Chinese population. The imputation-completed 100,000 microarray data are fundamental resources of population genetic studies for complex traits and diseases in the Chinese population.