Population-specific polygenic risk scores for people of Han Chinese ancestry

Predicting complex disease risks on the basis of individual genomic profiles is an advancing field in human genetics<sup>1,2</sup>. However, most genetic studies have focused on populations of European ancestry, creating a global imbalance in precision medicine and underscoring the need for genomic research in non-European groups<sup>3,4</sup>. The Taiwan Precision Medicine Initiative recruited more than half a million Taiwanese residents, providing a large dataset of genetic profiles and electronic medical record data for people with Han Chinese ancestry. Using extensive phenotypic data, we conducted comprehensive genomic analyses across the medical phenome with individuals genetically similar to Han Chinese reference populations. These analyses identified population-specific genetic risk variants and new findings for various complex traits. We developed polygenic risk scores, demonstrating strong predictive performance for conditions such as cardiometabolic diseases, autoimmune disorders, cancers and infectious diseases. We observed consistent findings in an independent dataset, Taiwan Biobank, and among people of East Asian ancestry in the UK Biobank and the All of Us Project. The identified genetic risks accounted for up to 10.3% of the overall health variation in the Taiwan Precision Medicine Initiative cohort. Our approach of characterizing the phenome-wide genomic landscape, developing population-specific risk-prediction models, assessing their performance and identifying the genetic effect on health serves as a model for similar studies in other diverse study populations.

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Journal
Nature
Published
2025-10-15
DOI
https://doi.org/10.1038/s41586-025-09350-y
Citations
10
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
18.17
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article

Population-specific polygenic risk scores for people of Han Chinese ancestry

Chia‐Hsin Chen, Ju‐Chi Liu, Jung‐Chun Lin, Ting‐Ting Yen et al.
10 citations
Nature
Genetic Associations and Epidemiology
18.17
article

Population-specific polygenic risk scores for people of Han Chinese ancestry

Chia‐Hsin Chen, Ju‐Chi Liu, Jung‐Chun Lin, Ting‐Ting Yen, Chi‐Cheng Li, Shu-Jung Chang, Wei‐Sheng Chen, Jing-Er Lee, Shih-Yao Lin, Chun-Yu Wei, Paul Chih-Hsueh Chen, Ping‐Han Tsai, Shi‐Heng Wang, Yi‐Lwun Ho, Jhih‐Syuan Liu, Stephen Hsu, Shun‐Fa Yang, Chun‐Houh Chen, Feng‐Jen Hsieh, Pui–Yan Kwok, An‐Chieh Feng, Ruiling Weng, Chih‐Yang Huang, Ming‐Chih Hou, Yi‐Chen Yeh, Lung‐Chang Lin, Cathy S.J. Fann, Yi‐Wei Yeh, Yi‐Jing Sheen, Chien-Lin Mao, Wayne Huey‐Herng Sheu, Kuo-Jang Kao, Tso‐Fu Wang, Hsin-Chien Yen, Ji‐Yuh Lee, Erh‐Chan Yeh, Sun‐Wung Hsieh, Jyh‐Ming Jimmy Juang, Chien-Hsiun Chen, Kung-Hao Liang, Elin H. F. Wang, Ming‐Shiang Wu, Chieh‐Hua Lu, Wan-Jia Lin, Po‐Yueh Chen, Gwo‐Chin Ma, I‐Hui Lee, Nain‐Feng Chu, I‐Chieh Chen, Hsin Tung, Jen-Ping Su, Kochung Tsui, Jeng‐Kai Jiang, Fu‐Tien Chiang, Jeng‐Fong Chiou, Jaw‐Yuan Wang, Hsueh-Ju Lu, Ling‐Hui Li, Jyh‐Ming Liou, Jia‐Horng Kao, Chun-Ping Chang, Ying‐Chin Lin, Ting‐Shuan Wu, Chung-Han Yang, Chih‐Hung Lai, Ming-Hwai Lin, Chih-Hsing Hung, Yi-Min Liu, Erik Widén, Hsiao‐Ting Chang, Yu‐Huei Huang, Chi‐Lu Chiang, Yu‐Cheng Hsieh, Yen-Lin Chang, Chih‐Yen Chien, Jiunn‐Wei Wang, Yen-Hung Lin, Wei-Cheng Tseng, Kuei‐Ying Su, Yen‐Tsung Huang, Bi-Zhen Kao, Chien‐Ping Chiang, Yung‐Ta Kao, Chi‐Li Chung, Chen‐Fang Hung, En Meng, Shun-Sheng Chen, Hung‐Hsin Chen, Hsin‐Chou Yang, Dong‐Ru Ho, Yen‐Bin Liu, I‐Chen Wu, Shen‐Liang Shih, Timothy G. Raben, Hung‐Cheng Tsai, Mei‐Hsiu Chen, Yi‐Ju Liao, Yiming Chen, Yuchang Lin, Yu‐Chi Chen, Wei‐Ming Li, Ming-Fang Tsai, Yen–Ju Chen, Wei‐Ju Lee, Jia-Kang Wang, Mingyao Chen, Ting‐Yu Chang, Hsiang‐Ling Ho, Yushu Huang, Tzu‐Hung Hsiao, Chengxiang Yang, Che-Yu Chou, Yen-Fu Chen, Marie Lin, Hsien-Ming Wu, Ching‐Heng Lin, Chang-Hsien Lin, Fu-Pang Chang, Ching‐Yao Tsai, Hua-Fen Chen, Paul H. Chan, Ling-Ming Tseng, Yun‐Ching Fu, Kuan-Gen Huang, Wen-Yih Liang, Yuan-Tsong Chen, Jer‐Yuarn Wu
article en
10 citations

Abstract

Predicting complex disease risks on the basis of individual genomic profiles is an advancing field in human genetics<sup>1,2</sup>. However, most genetic studies have focused on populations of European ancestry, creating a global imbalance in precision medicine and underscoring the need for genomic research in non-European groups<sup>3,4</sup>. The Taiwan Precision Medicine Initiative recruited more than half a million Taiwanese residents, providing a large dataset of genetic profiles and electronic medical record data for people with Han Chinese ancestry. Using extensive phenotypic data, we conducted comprehensive genomic analyses across the medical phenome with individuals genetically similar to Han Chinese reference populations. These analyses identified population-specific genetic risk variants and new findings for various complex traits. We developed polygenic risk scores, demonstrating strong predictive performance for conditions such as cardiometabolic diseases, autoimmune disorders, cancers and infectious diseases. We observed consistent findings in an independent dataset, Taiwan Biobank, and among people of East Asian ancestry in the UK Biobank and the All of Us Project. The identified genetic risks accounted for up to 10.3% of the overall health variation in the Taiwan Precision Medicine Initiative cohort. Our approach of characterizing the phenome-wide genomic landscape, developing population-specific risk-prediction models, assessing their performance and identifying the genetic effect on health serves as a model for similar studies in other diverse study populations.

NatureVol. 648(8092)
Fu Jen Catholic University (TW), Northeastern University (US), Tri-Service General Hospital (TW), National Sun Yat-sen University (TW), National Yang Ming Chiao Tung University (TW), Kaohsiung Medical University (TW), National Chung Hsing University (TW), National Health Research Institutes (TW), National Taiwan University (TW), Chang Gung University (TW), University of California, San Francisco (US), Tzu Chi University (TW), Ming Chuan University (TW), University of Taipei (TW), National Tsing Hua University (TW), Tzu Chi Foundation (TW), Taipei Medical University Hospital (TW), Kaohsiung Medical University Chung-Ho Memorial Hospital (TW), Taipei Veterans General Hospital (TW), Chang Gung Memorial Hospital (TW), Taipei Municipal YangMing Hospital (TW), Taichung Veterans General Hospital (TW), Taoyuan Chang Gung Memorial Hospital (TW), Kaohsiung Chang Gung Memorial Hospital (TW), Institute of Biomedical Sciences, Academia Sinica (TW), Far Eastern Memorial Hospital (TW), Chung Shan Medical University Hospital (TW), Chia-Yi Christian Hospital (TW), Linkou Chang Gung Memorial Hospital (TW), Taipei City Hospital (TW), Ministry of Health and Welfare (TW), Cathay General Hospital (TW), National Taiwan University Hospital (TW), Genomic Prediction (United States) (US), Koo Foundation Sun Yat-Sen Cancer Center (TW), Institute of Statistical Science, Academia Sinica (TW), Wan Fang Hospital (TW), Buddhist Tzu Chi Medical Foundation (US), Kaohsiung Municipal Hsiao-Kang Hospital (TW), Chiayi Chang Gung Memorial Hospital (TW), Taipei Medical University-Shuang Ho Hospital (TW), Changhua Christian Hospital (TW), Taipei Medical University (TW), National Defense Medical Center (TW), National Yunlin University of Science and Technology (TW), Academia Sinica (TW), Michigan State University (US), Vanderbilt University Medical Center (US), Chung Shan Medical University (TW), National Yang Ming Chiao Tung University (TW), Yuan Ze University (TW)
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Genetic Associations and Epidemiology
18.17
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