Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population
Authors: Shi Jianxin , Shiraishi Kouya , Choi Jiyeon , Matsuo Keitaro , Chen Tzu-Yu , Dai Juncheng , Hung Rayjean J. , Chen Kexin , Shu Xiao-Ou , Kim Young Tae , Landi Maria Teresa , Lin Dongxin , Zheng Wei , Yin Zhihua , Zhou Baosen , Song Bao , 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 , Funderburk Karen M. , Li Shilan , Zhang Tongwu , Breeze Charles , Wang Zhaoming , Blechter Batel , Bassig Bryan A. , Kim Jin Hee , Albanes Demetrius , Wong Jason Y. Y. , 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 , Ho James Chung Man , Kubo Michiaki , Daigo Yataro , Song Minsun , Momozawa Yukihide , Kamatani Yoichiro , Kobayashi Masashi , Okubo Kenichi , Honda Takayuki , Hosgood Dean H. , Kunitoh Hideo , Patel Harsh , 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 , Lee Victor Ho Fun , Chang Gee-Chen , Tsai Ying-Huang , Chen 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. , 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 , Sihoe Alan Dart Loon , 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. , Hsiung Chao Agnes , Amos Christopher I. , Shen Hongbing , Chanock Stephen J. , Rothman Nathaniel , Kohno Takashi , Lan Qing 
Published: May 2023

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.