Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population
Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Juncheng Dai, Rayjean J. Hung, Kexin Chen, Xiao‐Ou Shu, Young Tae Kim, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Bao Song, Jiucun Wang, Wei Jie Seow, Lei Song, I‐Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun‐Chul Hong, Hee Nam Kim, Yi‐Long Wu, Maria Pik Wong, Brian Richardson, Karen Funderburk, Shilan Li, Tongwu Zhang, Charles E. Breeze, Zhaoming Wang, Batel Blechter, Bryan A. Bassig, Jin Hee Kim, Demetrius Albanes, Jason Y.Y. Wong, Min‐Ho Shin, Lap Ping Chung, Yang Yang, Shejuan An, Hong Zheng, Yasushi Yatabe, Xu‐Chao Zhang, Young‐Chul Kim, Neil E. Caporaso, Jiang Chang, Jcm Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean Hosgood, Hideo Kunitoh, Harsh Patel, Shun‐ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Kōichi Goto, Yuichiro Ohe, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Hong Dai, Mitchell J. Machiela, Jian Su, Yeul Hong Kim, In‐Jae Oh, Victor Lee, Gee‐Chen Chang, Ying‐Huang Tsai, Kuan‐Yu Chen, Ming‐Shyan Huang, Wu‐Chou Su, Yuh‐Min Chen, Adeline Seow, Jae Yong Park, Sun‐Seog Kweon
Abstract
Abstract 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 (P interaction = 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.