Clinical impact of pharmacogenetic risk variants in a large chinese cohort
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.
Article Details
Authors (124)
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
Ordered Matter Science Research Center
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
Division of Nephrology, Department of Medicine, Far Eastern Memorial Hospital
Hsiang-Cheng Chen
Pui-Yan Kwok