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, Institute of Biomedical Sciences
Ming-Shien Wen: Linkou Branch, Division of Cardiology, Chang Gung Memorial Hospital
Chih-Kuang Cheng: Chang Gung Memorial Hospital, Linkou Branch, Department of Neurology
Yi-Jing Sheen: Taichung Veterans General Hospital, Division of Endocrinology and Metabolism, Department of Internal Medicine
Tsung-Chieh Yao: Chang Gung Memorial Hospital, Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics
Sing-Lian Lee: Koo Foundation Sun Yat-Sen Cancer Center, Department of Internal Medicine
Jer-Yuarn Wu: Academia Sinica, Institute of Biomedical Sciences
Ming-Fang Tsai: Academia Sinica, Institute of Biomedical Sciences
Ling-Hui Li: Academia Sinica, Institute of Biomedical Sciences
Chun-houh Chen: Academia Sinica, Institute of Statistical Science
Cathy S.-J. Fann: Academia Sinica, Institute of Biomedical Sciences
Hsin-Chou Yang: Academia Sinica, Institute of Statistical Science
Yen-Tsung Huang: Academia Sinica, Institute of Statistical Science
Hung-Hsin Chen: Academia Sinica, Institute of Biomedical Sciences
Yi-Min Liu: Academia Sinica, Institute of Biomedical Sciences
Erh-Chan Yeh: Academia Sinica, Institute of Biomedical Sciences
Yu-Ching Peng: Taipei Veterans General Hospital, Department of Pathology and Laboratory Medicine
Shuu-Jiun Wang: Taipei Veterans General Hospital, Department of Neurology, Neurological Institute
Shih-Pin Chen: Taipei Veterans General Hospital, Department of Neurology, Neurological Institute
Ming-Tsun Tsai: National Yang Ming Chiao Tung University, Institute of Clinical Medicine
Teh-Ia Huo: Taipei Veterans General Hospital, Division of Basic Research, Department of Medical Research
Chien-Wei Su: National Yang Ming Chiao Tung University, Institute of Clinical Medicine
Tarng Der-Cherng: Taipei Veterans General Hospital, Division of Nephrology, Department of Medicine
Chin-Chou Huang: National Yang Ming Chiao Tung University, Faculty of Medicine, School of Medicine
Jong-Ling Fuh: Taipei Veterans General Hospital, Department of Neurology, Neurological Institute
Keng-Hsin Lan: National Yang Ming Chiao Tung University, Institute of Pharmacology, College of Medicine
Yo-Tsen Liu: National Yang Ming Chiao Tung University, School of Medicine
Ching-Liang Lu: National Yang Ming Chiao Tung University, Faculty of Medicine, School of Medicine
Yi-Chung Lee: Taipei Veterans General Hospital, Department of Neurology, Neurological Institute
Yi-Hsiang Huang: Taipei Veterans General Hospital, Division of Gastroenterology and Hepatology, Department of Medicine
Chung-Pin Li: Taipei Veterans General Hospital, Division of Clinical Skills Training, Department of Medical Education
Yen-Feng Wang: Taipei Veterans General Hospital, Department of Neurology, Neurological Institute
Yu-Cheng Hsieh: National Chung Hsing University, Department of Post-Baccalaureate Medicine, College of Medicine
Yi-Ming Chen: National Chung Hsing University, Department of Post-Baccalaureate Medicine, College of Medicine
Tzu-Hung Hsiao: Taichung Veterans General Hospital, Department of Medical Research
Ching-Heng Lin: Taichung Veterans General Hospital, Department of Medical Research
Yen-Ju Chen: Taichung Veterans General Hospital, Department of Medical Research
I-Chieh Chen: Taichung Veterans General Hospital, Department of Medical Research
Chien-Lin Mao: Taichung Veterans General Hospital, Department of Medical Research
Shu-Jung Chang: Taichung Veterans General Hospital, Department of Medical Research
Yen-Lin Chang: Taichung Veterans General Hospital, Department of Pharmacy
Yi-Ju Liao: Taichung Veterans General Hospital, Department of Pharmacy
Chih-Hung Lai: Taichung Veterans General Hospital, Department of Medicine and Cardiovascular Center
Wei-Ju Lee: National Chung Hsing University, Department of Post-Baccalaureate Medicine, College of Medicine
Hsin Tung: National Chung Hsing University, Department of Post-Baccalaureate Medicine, College of Medicine
Ting-Ting Yen: Taichung Veterans General Hospital, Department of Otolaryngology
Hsin-Chien Yen: Taichung Veterans General Hospital, Division of Pediatric Genetics and Metabolism, Children’s Medical Center
Jer-Hwa Chang: Taipei Medical University, School of Respiratory Therapy, College of Medicine
Chun-Yao Huang: Taipei Medical University, Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine
Lung Chan: Taipei Medical University, Department of Neurology, Shuang Ho Hospital
Yung-Wei Lin: Taipei Medical University, Department of Urology, School of Medicine, College of Medicine and TMU Research Center of Urology and Kidney (TMU-RCUK)
Bu-Yuan Hsiao: Taipei Medical University, Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine
Chaur-Jong Hu: Taipei Medical University, Department of Neurology, Shuang Ho Hospital
Yung-Kuo Lin: Taipei Medical University, Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine
Yung-Feng Lin: Taipei Medical University Hospital, Department of Medicine Research
Tung-Cheng Chang: Taipei Medical University, Division of Colorectal Surgery, Department of Surgery, Shuang Ho Hospital
Deng-Chyang Wu: Kaohsiung Medical University, Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital
Jung-Yu Kan: Kaohsiung Medical University, Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital
Chung-Yao Hsu: Kaohsiung Medical University, Sleep Medicine Center, Department of Neurology, Kaohsiung Medical University Hospital
Szu-Chia Chen: Kaohsiung Medical University, Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital
Ching-Chia Li: Kaohsiung Medical University, Department of Urology, Kaohsiung Medical University Hospital
Chung-Feng Huang: Kaohsiung Medical University, Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital
Chau-Chyun Sheu: Kaohsiung Medical University, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital
Lii-Jia Yang: Kaohsiung Medical University, Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital
Chung-Hwan Chen: Kaohsiung Medical University, Orthopaedic Research Center and Department of Orthopedics, College of Medicine
Kuan-Mao Chen: Academia Sinica, Institute of Biomedical Sciences
Shu-Min Chang: Academia Sinica, Institute of Biomedical Sciences
Min-Shiuan Liou: Academia Sinica, Institute of Biomedical Sciences
Shi-Ping Wang: Academia Sinica, Institute of Biomedical Sciences
Kuan-Ting Lin: Academia Sinica, Institute of Biomedical Sciences
Hui-Ping Chuang: Academia Sinica, Institute of Biomedical Sciences
Ying-Ju Chen: Academia Sinica, Institute of Biomedical Sciences
Joey Sin: Academia Sinica, Institute of Biomedical Sciences
Ying-Ting Chen: Academia Sinica, Institute of Biomedical Sciences
Chiung-Chih Chang: Kaohsiung Chang Gung Memorial Hospital, Department of Neurology, Cognition and Aging Center
Chang-Fu Kuo: Chang Gung Memorial Hospital, Center for Artificial Intelligence in Medicine
Jing-Chi Lin: Chang Gung Memorial Hospital, Division of Allergy Immunology and Rheumatology
Ho-Chang Kuo: Kaohsiung Chang Gung Memorial Hospital, Pediatric Internal Medicine, Department of Internal Medicine
Tien-Min Chan: Chang Gung Memorial Hospital, Division of Rheumatology, Allergy and Immunology
Chao-Wei Lee: Linkou Chang Gung Memorial Hospital, Division of General Surgery, Department of Surgery
Jenn-Haung Lai: Chang Gung Memorial Hospital, Division of Rheumatology, Allergy and Immunology
Shue-Fen Luo: Linkou Chang Gung Memorial Hospital, Department of Rheumatology, Allergy and Immunology
Hao-Tsai Cheng: New Taipei Municipal TuCheng Hospital, Department of Gastroenterology and Hepatology
Lian-Yu Lin: National Taiwan University Hospital, Department of Internal Medicine
Li-Chun Chang: National Taiwan University Hospital, Department of Internal Medicine
Chia-Ti Tsai: National Taiwan University Hospital, Department of Internal Medicine
Hsien-Li Kao: National Taiwan University Hospital, Department of Internal Medicine
Jian-Jyun Yu: Yunlin Branch, Department of Internal Medicine, National Taiwan University Hospital
Jiann-Shing Jeng: National Taiwan University Hospital, Department of Neurology
Min-Chin Chiu: Yunlin Branch, Department of Internal Medicine, National Taiwan University Hospital
Tzu-Chan Hong: National Taiwan University College of Medicine, Department of Internal Medicine
Shun-Fa Yang: Chung Shan Medical University, Institute of Medicine
Hsueh-Ju Lu: Chung Shan Medical University Hospital, Division of Hematology and Oncology, Department of Internal Medicine
Sheng-Chiang Su: National Defense Medical Center, Endocrinology and Metabolism, Tri-Service General Hospital
Pauling Chu: National Defense Medical Center, Nephrology, Tri-Service General Hospital
Peng-Fei Li: National Defense Medical Center, Endocrinology and Metabolism, Tri-Service General Hospital
Chia-Lin Tsai: National Defense Medical Center, Neurology, Tri-Service General Hospital
Chia-Kuang Tsai: National Defense Medical Center, Neurology, Tri-Service General Hospital
Shih-En Tang: National Defense Medical Center, Pulmonary Medicine, Tri-Service General Hospital
Chien-Ming Lin: National Defense Medical Center, Pediatrics, Tri-Service General Hospital
Yung-Fu Wu: National Defense Medical Center, Department of Medical Research, Tri-Service General Hospital
Chih-Yang Huang: Buddhist Tzu Chi Medical Foundation, Cardiovascular and Mitochondria Related Disease Research Center, Hualien Tzu Chi Hospital
Shinn-Zong Ling: Buddhist Tzu Chi Medical Foundation, Bioinnovation Center
Chun-Chun Chang: Buddhist Tzu Chi Medical Foundation, Department of Laboratory Medicine, Hualien Tzu Chi Hospital
Tzu-Kai Lin: Buddhist Tzu Chi Medical Foundation, Department of Dermatology, Hualien Tzu Chi Hospital
Sheng-Mou Hsiao: Far Eastern Memorial Hospital, Department of Obstetrics and Gynecology
Chih-Hung Chang: Yuan Ze University, Graduate School of Biotechnology and Bioengineering
Chih-Dao Chen: Far Eastern Memorial Hospital, Department of Family Medicine
Gwo-Chin Ma: Changhua Christian Hospital, Department of Genomic Medicine and Center for Medical Genetics
Ting-Yu Chang: Changhua Christian Hospital, Department of Genomic Medicine and Center for Medical Genetics
Juey-Jen Hwang: Fu Jen Catholic University, Department of Cardiology, Fu Jen Catholic University Hospital
Chien-Lin Lu: Fu Jen Catholic University, School of Medicine, College of Medicine
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, Division of Urology
Po-Yueh Chen: Ditmanson Medical Foundation Chia-Yi Christian Hospital, Division of Gastroenterology and Hepatology, Department of Internal Medicine
Kochung Tsui: Fu-Jen Catholic University, School of Medicine
Yuan-Tsong Chen: Academia Sinica, Institute of Biomedical Sciences
Chien-Hsiun Chen: Academia Sinica, Institute of Biomedical Sciences
Chih-Cheng Chien: Fu-Jen Catholic University, School of Medicine
Han-Sun Chiang: Fu Jen Catholic University, School of Medicine, College of Medicine
Yen-Ling Chiu: Far Eastern Memorial Hospital, Department of Medical Research
Hsiang-Cheng Chen: Tri-Service General Hospital, Division of Rheumatology, Immunology and Allergy
Pui-Yan Kwok: Academia Sinica, Institute of Biomedical Sciences

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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