Population-Specific Polygenic Risk Scores Developed for the Han Chinese
Authors: Chen Hung-Hsin , Chen Chien-Hsiun , Hou Ming-Chih , Fu Yun-Ching , Li Ling-Hui , Chou Che-Yu , Yeh Erh-Chan , Tsai Ming-Fang , Chen Chun-houh , Yang Hsin-Chou , Huang Yen-Tsung , Liu Yi-Min , Wei Chun-yu , Su Jen-Ping , Lin Wan-Jia , Wang Elin H.F. , Chiang Chi-Lu , Jiang Jeng-Kai , Lee I-Hui , Liang Kung-Hao , Chen Wei-Sheng , Tsai Hung-Cheng , Lin Shih-Yao , Chang Fu-Pang , Ho Hsiang-Ling , Yeh Yi-Chen , Tseng Wei-Cheng , Lin Ming-Hwai , Chang Hsiao-Ting , Tseng Ling-Ming , Liang Wen-Yih , Chen Paul Chih-Hsueh , Hsieh Yu-Cheng , Chen Yi-Ming , Hsiao Tzu-Hung , Lin Ching_Heng , Chen Yen-Ju , Chen I-Chieh , Mao Chien-Lin , Chang Shu-Jung , Chang Yen-Lin , Liao Yi_Ju , Lai Chih-Hung , Lee Wei-Ju , Tung Hsin , Yen Ting-Ting , Yen Hsin-Chien , Chen Ming-Yao , Lin Ying-Chin , Kao Yung-Ta , Kao Bi-Zhen , Lee Jing-Er , Chung Chi-Li , Liu Ju-Chi , Chan Paul , Lin Chang-Hsien , Chia-Hsin Chen , Wu I-Chen , Lin Lung-Chang , Wang Jiunn-Wei , Shih Shen-liang , Hsieh Sun-Wung , Hung Chih-Hsing , Li Wei-Ming , Yang Chih-Jen , Yang Cheng-Shin , Weng Ru-Hui , Chen Yu-Chi , Chang Chun-Ping , Wu Tai-Hsun , Lin Yu-Chang , Sheen Yi-Jing , Wang Shi-Heng , Chen Sye-Pu , Raben Timothy , Widen Erik , Hsu Stephen , Hsieh Feng-Jen , Ho Dong-Ru , Huang Yu-Huei , Yang Chung-Han , Huang Yu-Shu , Chen Yen-Fu , Wu Hsien-Ming , Tsai Ping-Han , Huang Kuan-Gen , Chien Chih-Yen , Ho Yi-Lwun , Wu Ming-Shiang , Kao Jia-Horng , Liu Yen-Bin , Juang Jyh-Ming Jimmy , Lin Mao-Hsin , Lin Yen-Hung , Lee Ji-Yuh , Lu Hsueh-Ju , Lu Chieh-Hua , Feng An-Chieh , Liu Jhih-Syuan , Chiang Chien-Ping , Chu Nain-Feng , Lin Jung-Chun , Yeh Yi-Wei , Meng En , Huang Chih-Yang , Li Chi-Cheng , Wang Tso-Fu , Su Kuei-Ying , Wang Jia-Kang , Chen Mei-Hsiu , Chen Hua-Fen , Ma Gwo-Chin , Chang Ting-Yu , Chiang Fu-Tien , Chang Hsing-Jung , Kao Kuo-Jang , Hung Chen-Fang , Tsai Ching-Yao , Chen Po-Yueh , Tsui Kochung , Kwok Pui-Yan , Sheu Wayne Huey-Herng , Yang Shun-Fa , Liou Jyh-Ming , Wang Jaw-Yuan , Chiou Jeng-Fong , Wu Jer-Yuarn , Fann Cathy S.-J. 
Published: October 2024

AbstractPredicting complex disease risks based on individual genomic profiles is an advancing field in human genetics.1,2However, most genetic studies have focused on European populations, creating a global imbalance in precision medicine and underscoring the need for genomic research in non-European groups3,4. The Taiwan Precision Medicine Initiative (TPMI) recruited over half a million Taiwanese residents, providing the largest dataset of genetic profiles and electronic medical record data for the Han Chinese. Using extensive phenotypic data, we conducted the largest genomic analyses of Han Chinese across the medical phenome. These analyses identified population-specific genetic risk variants and novel findings on the genetic architecture of 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 sample from our Biobank and among East Asians in the UK Biobank and the All of Us Project. The identified genetic risks accounted for up to 9.1% of the disease burden variance in Taiwan. Our approach of characterizing the phenome-wide genomic landscape, developing population-specific risk prediction models, assessing their performance, and identifying the genetic impact on health, serves as a model for similar studies in other diverse study populations.