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 ChangWei Hu, Li Hsin Chien, Qiuyin Cai, Yun Chul Hong, Hee Nam Kim, Yi Long Wu, Maria Pik Wong, Brian Douglas Richardson, Karen M. Funderburk, Shilan Li, Tongwu Zhang, Charles 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, She Juan An, Hong Zheng, Yasushi Yatabe, Xu Chao Zhang, Young Chul Kim, Neil E. Caporaso, Jiang Chang, James Chung Man Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean H. Hosgood, Hideo Kunitoh, Harsh Patel, Shun ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi 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, Hongji Dai, Mitchell J. Machiela, Jian Su, Yeul Hong Kim, In Jae Oh, Victor Ho Fun 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, Kun Chieh Chen, Yu Tang Gao, Biyun Qian, Chen Wu, Daru Lu, Jianjun Liu, Ann G. Schwartz, Richard Houlston, Margaret R. Spitz, Ivan P. Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E. Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu Tian Ji, H. Erich Wichmann, David C. Christiani, Gadi Rennert, Susanne Arnold, Paul Brennan, James McKay, John K. Field, Sanjay S. Shete, Loic Le Marchand, Geoffrey Liu, Angeline Andrew, Lambertus A. Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Mikael Johansson, Angela Cox, Fiona Taylor, Jian Min Yuan, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Hyo Sung Jeon, Shih Sheng Jiang, Jae Sook Sung, Chung Hsing Chen, Chin Fu Hsiao, Yoo Jin Jung, Huan Guo, Zhibin Hu, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Bin Zhu, Sonja I. Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Wen Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho Il Yoon, In Kyu Park, Ping Xu, Qincheng He, Chih Liang Wang, Hsiao Han Hung, Roel C.H. Vermeulen, Iona Cheng, Junjie Wu, Wei Yen Lim, Fang Yu Tsai, John K.C. Chan, Jihua Li, Hongyan Chen, Hsien Chih Lin, Li Jin, Jie Liu, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Shengchao A. Li, Hongxia Ma, Meng Zhu, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Chih Yi Chen, Chien Jen Chen, Pan Chyr Yang, Jinming Yu, Victoria L. Stevens, Joseph F. Fraumeni, Nilanjan Chatterjee, Olga Y. Gorlova, Chao Agnes Hsiung, Christopher I. Amos, Hongbing Shen, Stephen J. Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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 (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.

Original languageEnglish
Article number3043
JournalNature communications
Volume14
Issue number1
DOIs
Publication statusPublished - 2023 Dec
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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