Imputation disparities driven by recent selection and their impact on disease risk estimation in East and Southeast Asian populations
1
Issued Date
2025-12-01
Resource Type
eISSN
23993642
Scopus ID
2-s2.0-105026163084
Journal Title
Communications Biology
Volume
8
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Communications Biology Vol.8 No.1 (2025)
Suggested Citation
Li D., Tangtanatakul P., Lei Y., Liu X., Huang H.Y., Lin Y.C.D., Li C., Chen Y., Cai L., Zhao J., Pisitkul P., Suangtamai T., Yu J., Zhou Y., Xu Y., Xiao Y., Kunhapan P., Sun R., Yu G., Sun H., Hirankarn N., Ishikawa Y., Terao C., Kim K., Bae S.C., Wang M., Huang H.D., Yang W., Wang Y.F. Imputation disparities driven by recent selection and their impact on disease risk estimation in East and Southeast Asian populations. Communications Biology Vol.8 No.1 (2025). doi:10.1038/s42003-025-09214-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113790
Title
Imputation disparities driven by recent selection and their impact on disease risk estimation in East and Southeast Asian populations
Author's Affiliation
The University of Hong Kong
Hanyang University
Kyung Hee University
Chulalongkorn University
The Chinese University of Hong Kong, Shenzhen
University of Shizuoka
Ramathibodi Hospital
Faculty of Medicine, Chulalongkorn University
Thailand Ministry of Public Health
Shenzhen Second People's Hospital
RIKEN Center for Integrative Medical Sciences
Shizuoka General Hospital
Hanyang University Hospital for Rheumatic Disease
Faculty of Allied Health Sciences
Hanyang University
Kyung Hee University
Chulalongkorn University
The Chinese University of Hong Kong, Shenzhen
University of Shizuoka
Ramathibodi Hospital
Faculty of Medicine, Chulalongkorn University
Thailand Ministry of Public Health
Shenzhen Second People's Hospital
RIKEN Center for Integrative Medical Sciences
Shizuoka General Hospital
Hanyang University Hospital for Rheumatic Disease
Faculty of Allied Health Sciences
Corresponding Author(s)
Other Contributor(s)
Abstract
Accurate genotype imputation is essential for large-scale genetic studies and precision medicine. While East Asian (EAS)-specific reference panels like ChinaMAP and CHN100k have been developed, most studies still rely on multi-ancestry panels like TOPMed due to the large sample size. However, their performance in underrepresented groups like Southeast Asians remains unclear. Using high-coverage whole-genome sequencing and SNP-array data from 8,316 Chinese and Thai individuals, we systematically evaluate six state-of-the-art reference panels for genotype imputation. Our results show that EAS-specific panels outperformed multi-ancestry panels for East and Southeast Asian populations. For example, ChinaMAP achieves a mean heterozygosity concordance rate above 0.90 without R<sup>2</sup> filtering, whereas TOPMed requires an R<sup>2</sup> threshold of 0.60-0.70 to achieve comparable results. Notably, we find that recent positive selection drives regional disparities in imputation accuracy, as illustrated by the olfactory receptor gene cluster. More importantly, our results indicate that the choice of reference panel and R<sup>2</sup> thresholds have a significant impact on polygenic risk score estimation for disease prediction. These findings provide valuable guidelines for improving genotype imputation in East and Southeast Asian populations and underscore the need for ancestrally diverse reference panels to support globally equitable genomic research.