Clinical impact of pharmacogenetic risk variants in a large chinese cohort

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 cli...

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Main Authors: 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, Der-Cherng Tarng, 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, Pui-Yan Kwok
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61644-x
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author 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
Der-Cherng Tarng
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
Pui-Yan Kwok
author_facet 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
Der-Cherng Tarng
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
Pui-Yan Kwok
author_sort Chun-Yu Wei
collection DOAJ
description 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.
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spelling doaj-art-b79f064757ae4467b43e4e2915b017522025-08-20T04:02:55ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-61644-xClinical impact of pharmacogenetic risk variants in a large chinese cohortChun-Yu Wei0Ming-Shien Wen1Chih-Kuang Cheng2Yi-Jing Sheen3Tsung-Chieh Yao4Sing-Lian Lee5Jer-Yuarn Wu6Ming-Fang Tsai7Ling-Hui Li8Chun-houh Chen9Cathy S.-J. Fann10Hsin-Chou Yang11Yen-Tsung Huang12Hung-Hsin Chen13Yi-Min Liu14Erh-Chan Yeh15Yu-Ching Peng16Shuu-Jiun Wang17Shih-Pin Chen18Ming-Tsun Tsai19Teh-Ia Huo20Chien-Wei Su21Der-Cherng Tarng22Chin-Chou Huang23Jong-Ling Fuh24Keng-Hsin Lan25Yo-Tsen Liu26Ching-Liang Lu27Yi-Chung Lee28Yi-Hsiang Huang29Chung-Pin Li30Yen-Feng Wang31Yu-Cheng Hsieh32Yi-Ming Chen33Tzu-Hung Hsiao34Ching-Heng Lin35Yen-Ju Chen36I-Chieh Chen37Chien-Lin Mao38Shu-Jung Chang39Yen-Lin Chang40Yi-Ju Liao41Chih-Hung Lai42Wei-Ju Lee43Hsin Tung44Ting-Ting Yen45Hsin-Chien Yen46Jer-Hwa Chang47Chun-Yao Huang48Lung Chan49Yung-Wei Lin50Bu-Yuan Hsiao51Chaur-Jong Hu52Yung-Kuo Lin53Yung-Feng Lin54Tung-Cheng Chang55Deng-Chyang Wu56Jung-Yu Kan57Chung-Yao Hsu58Szu-Chia Chen59Ching-Chia Li60Chung-Feng Huang61Chau-Chyun Sheu62Lii-Jia Yang63Chung-Hwan Chen64Kuan-Mao Chen65Shu-Min Chang66Min-Shiuan Liou67Shi-Ping Wang68Kuan-Ting Lin69Hui-Ping Chuang70Ying-Ju Chen71Joey Sin72Ying-Ting Chen73Chiung-Chih Chang74Chang-Fu Kuo75Jing-Chi Lin76Ho-Chang Kuo77Tien-Min Chan78Chao-Wei Lee79Jenn-Haung Lai80Shue-Fen Luo81Hao-Tsai Cheng82Lian-Yu Lin83Li-Chun Chang84Chia-Ti Tsai85Hsien-Li Kao86Jian-Jyun Yu87Jiann-Shing Jeng88Min-Chin Chiu89Tzu-Chan Hong90Shun-Fa Yang91Hsueh-Ju Lu92Sheng-Chiang Su93Pauling Chu94Peng-Fei Li95Chia-Lin Tsai96Chia-Kuang Tsai97Shih-En Tang98Chien-Ming Lin99Yung-Fu Wu100Chih-Yang Huang101Shinn-Zong Ling102Chun-Chun Chang103Tzu-Kai Lin104Sheng-Mou Hsiao105Chih-Hung Chang106Chih-Dao Chen107Gwo-Chin Ma108Ting-Yu Chang109Juey-Jen Hwang110Chien-Lin Lu111Kuo-Jang Kao112Chen-Fang Hung113Shiou-Sheng Chen114Po-Yueh Chen115Kochung Tsui116Yuan-Tsong Chen117Chien-Hsiun Chen118Chih-Cheng Chien119Han-Sun Chiang120Yen-Ling Chiu121Hsiang-Cheng Chen122Pui-Yan Kwok123Institute of Biomedical Sciences, Academia SinicaDivision of Cardiology, Chang Gung Memorial Hospital, Linkou BranchDepartment of Neurology, Chang Gung Memorial Hospital, Linkou BranchDivision of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General HospitalDivision of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial HospitalDepartment of Internal Medicine, Koo Foundation Sun Yat-Sen Cancer CenterInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Statistical Science, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Statistical Science, Academia SinicaInstitute of Statistical Science, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaDepartment of Pathology and Laboratory Medicine, Taipei Veterans General HospitalDepartment of Neurology, Neurological Institute, Taipei Veterans General HospitalDepartment of Neurology, Neurological Institute, Taipei Veterans General HospitalInstitute of Clinical Medicine, National Yang Ming Chiao Tung UniversityDivision of Basic Research, Department of Medical Research, Taipei Veterans General HospitalInstitute of Clinical Medicine, National Yang Ming Chiao Tung UniversityDivision of Nephrology, Department of Medicine, Taipei Veterans General HospitalFaculty of Medicine, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Neurology, Neurological Institute, Taipei Veterans General HospitalInstitute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung UniversitySchool of Medicine, National Yang Ming Chiao Tung UniversityFaculty of Medicine, School of Medicine, National Yang Ming Chiao Tung UniversityDepartment of Neurology, Neurological Institute, Taipei Veterans General HospitalDivision of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General HospitalDivision of Clinical Skills Training, Department of Medical Education, Taipei Veterans General HospitalDepartment of Neurology, Neurological Institute, Taipei Veterans General HospitalDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing UniversityDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing UniversityDepartment of Medical Research, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalDepartment of Medical Research, Taichung Veterans General HospitalDepartment of Pharmacy, Taichung Veterans General HospitalDepartment of Pharmacy, Taichung Veterans General HospitalDepartment of Medicine and Cardiovascular Center, Taichung Veterans General HospitalDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing UniversityDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing UniversityDepartment of Otolaryngology, Taichung Veterans General HospitalDivision of Pediatric Genetics and Metabolism, Children’s Medical Center, Taichung Veterans General HospitalSchool of Respiratory Therapy, College of Medicine, Taipei Medical UniversityDivision of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical UniversityDepartment of Neurology, Shuang Ho Hospital, Taipei Medical UniversityDepartment of Urology, School of Medicine, College of Medicine and TMU Research Center of Urology and Kidney (TMU-RCUK), Taipei Medical UniversityDivision of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical UniversityDepartment of Neurology, Shuang Ho Hospital, Taipei Medical UniversityDivision of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical UniversityDepartment of Medicine Research, Taipei Medical University HospitalDivision of Colorectal Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical UniversityDivision of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical UniversitySleep Medicine Center, Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDepartment of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityHepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDivision of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityOrthopaedic Research Center and Department of Orthopedics, College of Medicine, Kaohsiung Medical UniversityInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaDepartment of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial HospitalCenter for Artificial Intelligence in Medicine, Chang Gung Memorial HospitalDivision of Allergy Immunology and Rheumatology, Chang Gung Memorial HospitalPediatric Internal Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalDivision of Rheumatology, Allergy and Immunology, Chang Gung Memorial HospitalDivision of General Surgery, Department of Surgery, Linkou Chang Gung Memorial HospitalDivision of Rheumatology, Allergy and Immunology, Chang Gung Memorial HospitalDepartment of Rheumatology, Allergy and Immunology, Linkou Chang Gung Memorial HospitalDepartment of Gastroenterology and Hepatology, New Taipei Municipal TuCheng HospitalDepartment of Internal Medicine, National Taiwan University HospitalDepartment of Internal Medicine, National Taiwan University HospitalDepartment of Internal Medicine, National Taiwan University HospitalDepartment of Internal Medicine, National Taiwan University HospitalDepartment of Internal Medicine, National Taiwan University Hospital, Yunlin BranchDepartment of Neurology, National Taiwan University HospitalDepartment of Internal Medicine, National Taiwan University Hospital, Yunlin BranchDepartment of Internal Medicine, National Taiwan University College of MedicineInstitute of Medicine, Chung Shan Medical UniversityDivision of Hematology and Oncology, Department of Internal Medicine, Chung Shan Medical University HospitalEndocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical CenterNephrology, Tri-Service General Hospital, National Defense Medical CenterEndocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical CenterNeurology, Tri-Service General Hospital, National Defense Medical CenterNeurology, Tri-Service General Hospital, National Defense Medical CenterPulmonary Medicine, Tri-Service General Hospital, National Defense Medical CenterPediatrics, Tri-Service General Hospital, National Defense Medical CenterDepartment of Medical Research, Tri-Service General Hospital, National Defense Medical CenterCardiovascular and Mitochondria Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationBioinnovation Center, Buddhist Tzu Chi Medical FoundationDepartment of Laboratory Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationDepartment of Dermatology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationDepartment of Obstetrics and Gynecology, Far Eastern Memorial HospitalGraduate School of Biotechnology and Bioengineering, Yuan Ze UniversityDepartment of Family Medicine, Far Eastern Memorial HospitalDepartment of Genomic Medicine and Center for Medical Genetics, Changhua Christian HospitalDepartment of Genomic Medicine and Center for Medical Genetics, Changhua Christian HospitalDepartment of Cardiology, Fu Jen Catholic University Hospital, Fu Jen Catholic UniversitySchool of Medicine, College of Medicine, Fu Jen Catholic UniversityKoo Foundation Sun Yat-Sen Cancer CenterKoo Foundation Sun Yat-Sen Cancer CenterDivision of Urology, Taipei City Hospital Ren Ai BranchDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian HospitalSchool of Medicine, Fu-Jen Catholic UniversityInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaSchool of Medicine, Fu-Jen Catholic UniversitySchool of Medicine, College of Medicine, Fu Jen Catholic UniversityDepartment of Medical Research, Far Eastern Memorial HospitalDivision of Rheumatology, Immunology and Allergy, Tri-Service General HospitalInstitute of Biomedical Sciences, Academia SinicaAbstract 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.https://doi.org/10.1038/s41467-025-61644-x
spellingShingle 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
Der-Cherng Tarng
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
Pui-Yan Kwok
Clinical impact of pharmacogenetic risk variants in a large chinese cohort
Nature Communications
title Clinical impact of pharmacogenetic risk variants in a large chinese cohort
title_full Clinical impact of pharmacogenetic risk variants in a large chinese cohort
title_fullStr Clinical impact of pharmacogenetic risk variants in a large chinese cohort
title_full_unstemmed Clinical impact of pharmacogenetic risk variants in a large chinese cohort
title_short Clinical impact of pharmacogenetic risk variants in a large chinese cohort
title_sort clinical impact of pharmacogenetic risk variants in a large chinese cohort
url https://doi.org/10.1038/s41467-025-61644-x
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