Clinical Impact of Pharmacogenetic Risk Variants in a Large Chinese Cohort
Authors: Wei Chun-Yu , Wen Ming-Shien , Cheng Chih-Kuang , Sheen Yi-Jing , Yao Tsung-Chieh , Lee Sing-Lian , Wu Jer-Yuarn , Tsai Ming-Fang , Li Ling-Hui , Chen Chun-Houh , Fann Cathy S.-J. , Yang Hsin-Chou , Huang Yen-Tsung , Chen Hung-Hsin , Liu Yi-Min , Yeh Erh-Chan , Peng Yu-Ching , Wang Shuu-Jiun , Chen Shih-Pin , Tsai Ming-Tsun , Huo Teh-Ia , Su Chien-Wei , Tarng Der-Cherng , Huang Chin-Chou , Fuh Jong-Ling , Lan Keng-Hsin , Liu Yo-Tsen , Lu Ching-Liang , Lee Yi-Chung , Huang Yi-Hsiang , Li Chung-Pin , Wang Yen-Feng , 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 , Chang Jer-Hwa , Huang Chun-Yao , Chan Lung , Lin Yung-Wei , Hsiao Bu-Yuan , Hu Chaur-Jong , Lin Yung-Kuo , Lin Yung-Feng , Chang Tung-Cheng , Wu Deng-Chyang , Kan Jung-Yu , Hsu Chung-Yao , Chen Szu-Chia , Li Ching-Chia , Huang Chung-Feng , Sheu Chau-Chyun , Yang Lii-Jia , Chen Chung-Hwan , Chen Kuan-Mao , Chang Shu-Min , Liou Min-Shiuan , Wang Shi-Ping , Lin Kuan-Ting , Chuang Hui-Ping , Chen Ying-Ju , Sin Joey , Chen Ying-Ting , Chang Chiung-Chih , Kuo Chang-Fu , Lin Jing-Chi , Kuo Ho-Chang , Chan Tien-Min , Lee Chao-Wei , Lai Jenn-Haung , Luo Shue-Fen , Cheng Hao-Tsai , Lin Lian-Yu , Chang Li-Chun , Tsai Chia-Ti , Kao Hsien-Li , Yu Jian-Jyun , Jeng Jiann-Shing , Chiu Min-Chin , Hong Tzu-Chan , Yang Shun-Fa , Lu Hsueh-Ju , Su Sheng-Chiang , Chu Pau-Ling , Li Peng-Fei , Tsai Chia-Lin , Tsai Chia-Kuang , Tang Shih-En , Lin Chien-Ming , Wu Yung-Fu , Huang Chih-Yang , Ling Shinn-Zong , Chang Chun-Chun , Lin Tzu-Kai , Hsiao Sheng-Mou , Chang Chih-Hung , Chen Chih-Dao , Ma Gwo-Chin , Chang Ting-Yu , Hwang Juey-Jen , Lu Chien-Lin , Kao Kuo-Jang , Hung Chen-Fang , Chen Shiou-Sheng , Chen Po-Yueh , Tsui Ko-Chung , Chen Chien-Hsiun , Chien Chih-Cheng , Chiang Han-Sun , Chiu Yen-Ling , Chen Hsiang-Cheng , Kwok Pui-Yan 
Published: October 2024

ABSTRACTIncorporating pharmacogenetics into clinical practice promises to improve therapeutic outcome by choosing the medication and dosage optimized for a patient based on genetic factors that affect drug response1. One of the most promising benefits of PGx-guided therapy is the avoidance of adverse reactions2. To evaluate the clinical impact of PGx risk variants on adverse outcomes, we performed a retrospective study and analyzed the genetic and clinical data from the largest Han Chinese cohort 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 that detailed analyses of four gene-drug pairs, for which sufficient data exist for statistical power, validate previous findings that PGx risk variants are significantly associated with drug-related adverse events or ineffectiveness. However, the excess risk of side effects 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 need for identifying additional risk factors that cause adverse events in patients without PGx risk variants and factors that protect those with PGx risk variants from adverse events.