Nature Communications (May 2023)

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 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

DOI
https://doi.org/10.1038/s41467-023-38196-z
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 17

Abstract

Read online

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.