Clinical impact of pharmacogenetic risk variants in a large chinese cohort

Chun-Yu Wei (), Ming-Shien Wen, Chih-Kuang Cheng, Yi-Jing Sheen, Tsung-Chieh Yao, Sing-Lian Lee, Jer-Yuarn Wu, Ming-Fang Tsai, Ling-Hui Li, Chun-houh Chen, Cathy S.-J. Fann, Hsin-Chou Yang, Yen-Tsung Huang, Hung-Hsin Chen, Yi-Min Liu, Erh-Chan Yeh, Yu-Ching Peng, Shuu-Jiun Wang, Shih-Pin Chen, Ming-Tsun Tsai, Teh-Ia Huo, Chien-Wei Su, Tarng Der-Cherng, Chin-Chou Huang, Jong-Ling Fuh, Keng-Hsin Lan, Yo-Tsen Liu, Ching-Liang Lu, Yi-Chung Lee, Yi-Hsiang Huang, Chung-Pin Li, Yen-Feng Wang, Yu-Cheng Hsieh, Yi-Ming Chen, Tzu-Hung Hsiao, Ching-Heng Lin, Yen-Ju Chen, I-Chieh Chen, Chien-Lin Mao, Shu-Jung Chang, Yen-Lin Chang, Yi-Ju Liao, Chih-Hung Lai, Wei-Ju Lee, Hsin Tung, Ting-Ting Yen, Hsin-Chien Yen, Jer-Hwa Chang, Chun-Yao Huang, Lung Chan, Yung-Wei Lin, Bu-Yuan Hsiao, Chaur-Jong Hu, Yung-Kuo Lin, Yung-Feng Lin, Tung-Cheng Chang, Deng-Chyang Wu, Jung-Yu Kan, Chung-Yao Hsu, Szu-Chia Chen, Ching-Chia Li, Chung-Feng Huang, Chau-Chyun Sheu, Lii-Jia Yang, Chung-Hwan Chen, Kuan-Mao Chen, Shu-Min Chang, Min-Shiuan Liou, Shi-Ping Wang, Kuan-Ting Lin, Hui-Ping Chuang, Ying-Ju Chen, Joey Sin, Ying-Ting Chen, Chiung-Chih Chang, Chang-Fu Kuo, Jing-Chi Lin, Ho-Chang Kuo, Tien-Min Chan, Chao-Wei Lee, Jenn-Haung Lai, Shue-Fen Luo, Hao-Tsai Cheng, Lian-Yu Lin, Li-Chun Chang, Chia-Ti Tsai, Hsien-Li Kao, Jian-Jyun Yu, Jiann-Shing Jeng, Min-Chin Chiu, Tzu-Chan Hong, Shun-Fa Yang, Hsueh-Ju Lu, Sheng-Chiang Su, Pauling Chu, Peng-Fei Li, Chia-Lin Tsai, Chia-Kuang Tsai, Shih-En Tang, Chien-Ming Lin, Yung-Fu Wu, Chih-Yang Huang, Shinn-Zong Ling, Chun-Chun Chang, Tzu-Kai Lin, Sheng-Mou Hsiao, Chih-Hung Chang, Chih-Dao Chen, Gwo-Chin Ma, Ting-Yu Chang, Juey-Jen Hwang, Chien-Lin Lu, Kuo-Jang Kao, Chen-Fang Hung, Shiou-Sheng Chen, Po-Yueh Chen, Kochung Tsui, Yuan-Tsong Chen, Chien-Hsiun Chen (), Chih-Cheng Chien (), Han-Sun Chiang (), Yen-Ling Chiu (), Hsiang-Cheng Chen () and Pui-Yan Kwok ()
Additional contact information
Chun-Yu Wei: Academia Sinica
Ming-Shien Wen: Linkou Branch
Chih-Kuang Cheng: Chang Gung Memorial Hospital, Linkou Branch
Yi-Jing Sheen: Taichung Veterans General Hospital
Tsung-Chieh Yao: Chang Gung Memorial Hospital
Sing-Lian Lee: Koo Foundation Sun Yat-Sen Cancer Center
Jer-Yuarn Wu: Academia Sinica
Ming-Fang Tsai: Academia Sinica
Ling-Hui Li: Academia Sinica
Chun-houh Chen: Academia Sinica
Cathy S.-J. Fann: Academia Sinica
Hsin-Chou Yang: Academia Sinica
Yen-Tsung Huang: Academia Sinica
Hung-Hsin Chen: Academia Sinica
Yi-Min Liu: Academia Sinica
Erh-Chan Yeh: Academia Sinica
Yu-Ching Peng: Taipei Veterans General Hospital
Shuu-Jiun Wang: Taipei Veterans General Hospital
Shih-Pin Chen: Taipei Veterans General Hospital
Ming-Tsun Tsai: National Yang Ming Chiao Tung University
Teh-Ia Huo: Taipei Veterans General Hospital
Chien-Wei Su: National Yang Ming Chiao Tung University
Tarng Der-Cherng: Taipei Veterans General Hospital
Chin-Chou Huang: National Yang Ming Chiao Tung University
Jong-Ling Fuh: Taipei Veterans General Hospital
Keng-Hsin Lan: National Yang Ming Chiao Tung University
Yo-Tsen Liu: National Yang Ming Chiao Tung University
Ching-Liang Lu: National Yang Ming Chiao Tung University
Yi-Chung Lee: Taipei Veterans General Hospital
Yi-Hsiang Huang: Taipei Veterans General Hospital
Chung-Pin Li: Taipei Veterans General Hospital
Yen-Feng Wang: Taipei Veterans General Hospital
Yu-Cheng Hsieh: National Chung Hsing University
Yi-Ming Chen: National Chung Hsing University
Tzu-Hung Hsiao: Taichung Veterans General Hospital
Ching-Heng Lin: Taichung Veterans General Hospital
Yen-Ju Chen: Taichung Veterans General Hospital
I-Chieh Chen: Taichung Veterans General Hospital
Chien-Lin Mao: Taichung Veterans General Hospital
Shu-Jung Chang: Taichung Veterans General Hospital
Yen-Lin Chang: Taichung Veterans General Hospital
Yi-Ju Liao: Taichung Veterans General Hospital
Chih-Hung Lai: Taichung Veterans General Hospital
Wei-Ju Lee: National Chung Hsing University
Hsin Tung: National Chung Hsing University
Ting-Ting Yen: Taichung Veterans General Hospital
Hsin-Chien Yen: Taichung Veterans General Hospital
Jer-Hwa Chang: Taipei Medical University
Chun-Yao Huang: Taipei Medical University
Lung Chan: Taipei Medical University
Yung-Wei Lin: Taipei Medical University
Bu-Yuan Hsiao: Taipei Medical University
Chaur-Jong Hu: Taipei Medical University
Yung-Kuo Lin: Taipei Medical University
Yung-Feng Lin: Taipei Medical University Hospital
Tung-Cheng Chang: Taipei Medical University
Deng-Chyang Wu: Kaohsiung Medical University
Jung-Yu Kan: Kaohsiung Medical University
Chung-Yao Hsu: Kaohsiung Medical University
Szu-Chia Chen: Kaohsiung Medical University
Ching-Chia Li: Kaohsiung Medical University
Chung-Feng Huang: Kaohsiung Medical University
Chau-Chyun Sheu: Kaohsiung Medical University
Lii-Jia Yang: Kaohsiung Medical University
Chung-Hwan Chen: Kaohsiung Medical University
Kuan-Mao Chen: Academia Sinica
Shu-Min Chang: Academia Sinica
Min-Shiuan Liou: Academia Sinica
Shi-Ping Wang: Academia Sinica
Kuan-Ting Lin: Academia Sinica
Hui-Ping Chuang: Academia Sinica
Ying-Ju Chen: Academia Sinica
Joey Sin: Academia Sinica
Ying-Ting Chen: Academia Sinica
Chiung-Chih Chang: Kaohsiung Chang Gung Memorial Hospital
Chang-Fu Kuo: Chang Gung Memorial Hospital
Jing-Chi Lin: Chang Gung Memorial Hospital
Ho-Chang Kuo: Kaohsiung Chang Gung Memorial Hospital
Tien-Min Chan: Chang Gung Memorial Hospital
Chao-Wei Lee: Linkou Chang Gung Memorial Hospital
Jenn-Haung Lai: Chang Gung Memorial Hospital
Shue-Fen Luo: Linkou Chang Gung Memorial Hospital
Hao-Tsai Cheng: New Taipei Municipal TuCheng Hospital
Lian-Yu Lin: National Taiwan University Hospital
Li-Chun Chang: National Taiwan University Hospital
Chia-Ti Tsai: National Taiwan University Hospital
Hsien-Li Kao: National Taiwan University Hospital
Jian-Jyun Yu: Yunlin Branch
Jiann-Shing Jeng: National Taiwan University Hospital
Min-Chin Chiu: Yunlin Branch
Tzu-Chan Hong: National Taiwan University College of Medicine
Shun-Fa Yang: Chung Shan Medical University
Hsueh-Ju Lu: Chung Shan Medical University Hospital
Sheng-Chiang Su: National Defense Medical Center
Pauling Chu: National Defense Medical Center
Peng-Fei Li: National Defense Medical Center
Chia-Lin Tsai: National Defense Medical Center
Chia-Kuang Tsai: National Defense Medical Center
Shih-En Tang: National Defense Medical Center
Chien-Ming Lin: National Defense Medical Center
Yung-Fu Wu: National Defense Medical Center
Chih-Yang Huang: Buddhist Tzu Chi Medical Foundation
Shinn-Zong Ling: Buddhist Tzu Chi Medical Foundation
Chun-Chun Chang: Buddhist Tzu Chi Medical Foundation
Tzu-Kai Lin: Buddhist Tzu Chi Medical Foundation
Sheng-Mou Hsiao: Far Eastern Memorial Hospital
Chih-Hung Chang: Yuan Ze University
Chih-Dao Chen: Far Eastern Memorial Hospital
Gwo-Chin Ma: Changhua Christian Hospital
Ting-Yu Chang: Changhua Christian Hospital
Juey-Jen Hwang: Fu Jen Catholic University
Chien-Lin Lu: Fu Jen Catholic University
Kuo-Jang Kao: Koo Foundation Sun Yat-Sen Cancer Center
Chen-Fang Hung: Koo Foundation Sun Yat-Sen Cancer Center
Shiou-Sheng Chen: Taipei City Hospital Ren Ai Branch
Po-Yueh Chen: Ditmanson Medical Foundation Chia-Yi Christian Hospital
Kochung Tsui: Fu-Jen Catholic University
Yuan-Tsong Chen: Academia Sinica
Chien-Hsiun Chen: Academia Sinica
Chih-Cheng Chien: Fu-Jen Catholic University
Han-Sun Chiang: Fu Jen Catholic University
Yen-Ling Chiu: Far Eastern Memorial Hospital
Hsiang-Cheng Chen: Tri-Service General Hospital
Pui-Yan Kwok: Academia Sinica

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Incorporating pharmacogenetics into clinical practice promises to improve therapeutic outcomes by optimizing drug selection and dosage based on genetic factors affecting drug response. A key advantage of PGx-guided therapy is to decrease the likelihood of adverse events. To evaluate the clinical impact of PGx risk variants, we performed a retrospective study using genetic and clinical data from the largest Han Chinese cohort, comprising 486,956 individuals, assembled by the Taiwan Precision Medicine Initiative. We found that nearly all participants carried at least one genetic variant that could affect drug response, with many carrying multiple risk variants. Here we show the detailed analyses of four gene-drug pairs, azathioprine (NUDT15/TPMT), clopidogrel (CYP2C19), statins (ABCG2/CYP2C9/SLCO1B1), and NSAIDs (CYP2C9), for which sufficient data exists for statistical power. While the results validate previous findings that PGx risk variants are significantly associated with drug-related adverse events or ineffectiveness, the excess risk of adverse events or lack of efficacy is small compared to that found in those without the PGx risk variants, and most patients with PGx variants do not suffer from adverse events. Our results point to the complexity of implementing PGx in clinical practice and the need for integrative approaches to optimize precision medicine.

Date: 2025
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DOI: 10.1038/s41467-025-61644-x

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