Deep WGS-based STROMICS reference panel enhances genotype imputation in Chinese population

Abstract Genotype imputation is essential for medical genomics studies. Herein, we present the STROMICS imputation reference panel, constructed from high-depth whole-genome sequencing (WGS) data of 10,241 Chinese individuals. It includes 53,061,655 single-nucleotide variants and insertion-deletions, spanning 22 autosomes and the X chromosome. Imputation performance of the STROMICS and seven other reference panels was compared using WGS data from 159 individuals. STROMICS panel outperformed others in imputation quality, and in genome-wide population- and individual-level accuracy. Validation using 301 Chinese individuals from the 1000 Genomes Project demonstrated STROMICS achieving high imputation accuracy. Among the three Chinese subgroups, the STROMICS reference panel yielded the highest accuracy in Han Chinese in Beijing samples. Notably, STROMICS outperformed all the other panels for the insertion-deletion imputation. When imputing stroke-risk variants and their closely linked variants with STROMICS, only a small statistically significant difference in sensitivity was observed between diseased and healthy individuals for variants closely linked to stroke-risk variants. Furthermore, calculated using pruned variants, the genetic distances between diseased and healthy groups remained largely unchanged before and after imputation. Collectively, these findings indicate that the source material used to construct the STROMICS reference panel has minimal impact on its imputation performance. Finally, we demonstrated high accuracy of STROMICS for genotype imputation in the X-unique region. In conclusion, the STROMICS panel provides a high-quality reference for imputing genotypes across autosomes and the X chromosome in the Chinese population.