Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers
Authors: Blechter Batel , Wang Xiaoyu , Shi Jianxin , Shiraishi Kouya , Choi Jiyeon , Matsuo Keitaro , Chen Tzu-Yu , Dai Juncheng , Hung Rayjean J , Chen Kexin , Shu Xiao-Ou , Kim Young Tae , Choudhury Parichoy Pal , Williams Jacob , Landi Maria Teresa , Lin Dongxin , Zheng Wei , Yin Zhihua , Zhou Baosen , Wang Jiucun , Seow Wei Jie , Song Lei , Chang I-Shou , Hu Wei , Chien Li-Hsin , Cai Qiuyin , Hong Yun-Chul , Kim Hee Nam , Wu Yi-Long , Wong Maria Pik , Richardson Brian Douglas , Li Shilan , Zhang Tongwu , Breeze Charles , Wang Zhaoming , Bassig Bryan A , Kim Jin Hee , Albanes Demetrius , Wong Jason YY , Shin Min-Ho , Chung Lap Ping , Yang Yang , An She-Juan , Zheng Hong , Yatabe Yasushi , Zhang Xu-Chao , Kim Young-Chul , Caporaso Neil E , Chang Jiang , Man Ho James Chung , Kubo Michiaki , Daigo Yataro , Song Minsun , Momozawa Yukihide , Kamatani Yoichiro , Kobayashi Masashi , Okubo Kenichi , Honda Takayuki , Hosgood H Dean , Kunitoh Hideo , Watanabe Shun-ichi , Miyagi Yohei , Nakayama Haruhiko , Matsumoto Shingo , Horinouchi Hidehito , Tsuboi Masahiro , Hamamoto Ryuji , Goto Koichi , Ohe Yuichiro , Takahashi Atsushi , Goto Akiteru , Minamiya Yoshihiro , Hara Megumi , Nishida Yuichiro , Takeuchi Kenji , Wakai Kenji , Matsuda Koichi , Murakami Yoshinori , Shimizu Kimihiro , Suzuki Hiroyuki , Saito Motonobu , Ohtaki Yoichi , Tanaka Kazumi , Wu Tangchun , Wei Fusheng , Dai Hongji , Machiela Mitchell J , Su Jian , Kim Yeul Hong , Oh In-Jae , Fun Lee Victor Ho , Chang Gee-Chen , Tsai Ying-Huang , Che Kuan-Yu , Huang Ming-Shyan , Su Wu-Chou , Chen Yuh-Min , Seow Adeline , Park Jae Yong , Kweon Sun-Seog , Chen Kun-Chieh , Gao Yu-Tang , Qian Biyun , Wu Chen , Lu Daru , Liu Jianjun , Schwartz Ann G , Houlston Richard , Spitz Margaret R , Gorlov Ivan P , Wu Xifeng , Yang Ping , Lam Stephen , Tardon Adonina , Chen Chu , Bojesen Stig E , Johansson Mattias , Risch Angela , Bickeböller Heike , Ji Bu-Tian , Wichmann H-Erich , Christiani David C. , Rennert Gadi , Arnold Susanne , Brennan Paul , McKay James , Field John K , Davies Michael P.A. , Shete Sanjay S , Le Marchand Loic , Liu Geoffrey , Andrew Angeline , Kiemeney Lambertus A , Zienolddiny-Narui Shan , Grankvist Kjell , Johansson Mikael , Cox Angela , Taylor Fiona , Yuan Jian-Min , Lazarus Philip , Schabath Matthew B , Aldrich Melinda C , Jeon Hyo-Sung , Jiang Shih Sheng , Sung Jae Sook , Chen Chung-Hsing , Hsiao Chin-Fu , Jung Yoo Jin , Guo Huan , Hu Zhibin , Burdett Laurie , Yeager Meredith , Hutchinson Amy , Hicks Belynda , Liu Jia , Zhu Bin , Berndt Sonja I , Wu Wei , Wang Junwen , Li Yuqing , Choi Jin Eun , Park Kyong Hwa , Sung Sook Whan , Liu Li , Kang Chang Hyun , Wang Wen-Chang , Xu Jun , Guan Peng , Tan Wen , Yu Chong-Jen , Yang Gong , Loon Sihoe Alan Dart , Chen Ying , Choi Yi Young , Kim Jun Suk , Yoon Ho-Il , Park In Kyu , Xu Ping , He Qincheng , Wang Chih-Liang , Hung Hsiao-Han , Vermeulen Roel C.H. , Cheng Iona , Wu Junjie , Lim Wei-Yen , Tsai Fang-Yu , Chan John K.C. , Li Jihua , Chen Hongyan , Lin Hsien-Chih , Jin Li , Liu Jie , Sawada Norie , Yamaji Taiki , Wyatt Kathleen , Li Shengchao A. , Ma Hongxia , Zhu Meng , Wang Zhehai , Cheng Sensen , Li Xuelian , Ren Yangwu , Chao Ann , Iwasaki Motoki , Zhu Junjie , Jiang Gening , Fei Ke , Wu Guoping , Chen Chih-Yi , Chen Chien-Jen , Yang Pan-Chyr , Yu Jinming , Stevens Victoria L. , Fraumeni Joseph F. , Chatterjee Nilanjan , Gorlova Olga Y , Amos Christopher I , Shen Hongbing , Hsiung Chao Agnes , Chanock Stephen J , Rothman Nathaniel , Kohno Takashi , Lan Qing , Zhang Haoyu 
Published: June 2024

Polygenic risk scores (PRSs) are promising for risk stratification but have mainly been developed in European populations. This study developed single- and multi-ancestry PRSs for lung adenocarcinoma (LUAD) in East Asian (EAS) never-smokers using genome-wide association study summary statistics from EAS (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. A multi-ancestry PRS, developed using CT-SLEB, was strongly associated with LUAD risk (odds ratio=1.71, 95% confidence interval (CI):1.61,1.82), with an area under the receiver operating curve value of 0.640 (95% CI:0.629,0.653). Individuals in the highest 20% of the PRS had nearly four times the risk compared to the lowest 20%. Individuals in the 95thpercentile of the PRS had an estimated 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41. Our study underscores the potential of multi-ancestry PRS approaches to enhance LUAD risk stratification in EAS never-smokers.