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:10.1038/s41467-023-38196-z

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

Epidemiology & Population Health

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Article number	3043
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-38196-z
State	Published - Dec 2023

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-023-38196-z

Cite this

Shi, J., Shiraishi, K., Choi, J., Matsuo, K., Chen, T. Y., Dai, J., Hung, R. J., Chen, K., Shu, X. O., Kim, Y. T., Landi, M. T., Lin, D., Zheng, W., Yin, Z., Zhou, B., Song, B., Wang, J., Seow, W. J., Song, L., ... Lan, Q. (2023). Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population. Nature communications, 14(1), Article 3043. https://doi.org/10.1038/s41467-023-38196-z

Shi, J, Shiraishi, K, Choi, J, Matsuo, K, Chen, TY, Dai, J, Hung, RJ, Chen, K, Shu, XO, Kim, YT, Landi, MT, Lin, D, Zheng, W, Yin, Z, Zhou, B, Song, B, Wang, J, Seow, WJ, Song, L, Chang, IS, Hu, W, Chien, LH, Cai, Q, Hong, YC, Kim, HN, Wu, YL, Wong, MP, Richardson, BD, Funderburk, KM, Li, S, Zhang, T, Breeze, C, Wang, Z, Blechter, B, Bassig, BA, Kim, JH, Albanes, D, Wong, JYY, Shin, MH, Chung, LP, Yang, Y, An, SJ, Zheng, H, Yatabe, Y, Zhang, XC, Kim, YC, Caporaso, NE, Chang, J, Ho, JCM, Kubo, M, Daigo, Y, Song, M, Momozawa, Y, Kamatani, Y, Kobayashi, M, Okubo, K, Honda, T, Hosgood, DH, Kunitoh, H, Patel, H, Watanabe, SI, Miyagi, Y, Nakayama, H, Matsumoto, S, Horinouchi, H, Tsuboi, M, Hamamoto, R, Goto, K, Ohe, Y, Takahashi, A, Goto, A, Minamiya, Y, Hara, M, Nishida, Y, Takeuchi, K, Wakai, K, Matsuda, K, Murakami, Y, Shimizu, K, Suzuki, H, Saito, M, Ohtaki, Y, Tanaka, K, Wu, T, Wei, F, Dai, H, Machiela, MJ, Su, J, Kim, YH, Oh, IJ, Lee, VHF, Chang, GC, Tsai, YH, Chen, KY, Huang, MS, Su, WC, Chen, YM, Seow, A, Park, JY, Kweon, SS, Chen, KC, Gao, YT, Qian, B, Wu, C, Lu, D, Liu, J, Schwartz, AG, Houlston, R, Spitz, MR, Gorlov, IP, Wu, X, Yang, P, Lam, S, Tardon, A, Chen, C, Bojesen, SE, Johansson, M, Risch, A, Bickeböller, H, Ji, BT, Wichmann, HE, Christiani, DC, Rennert, G, Arnold, S, Brennan, P, McKay, J, Field, JK, Shete, SS, Le Marchand, L, Liu, G, Andrew, A, Kiemeney, LA, Zienolddiny-Narui, S, Grankvist, K, Johansson, M, Cox, A, Taylor, F, Yuan, JM, Lazarus, P, Schabath, MB, Aldrich, MC, Jeon, HS, Jiang, SS, Sung, JS, Chen, CH, Hsiao, CF, Jung, YJ, Guo, H, Hu, Z, Burdett, L, Yeager, M, Hutchinson, A, Hicks, B, Liu, J, Zhu, B, Berndt, SI, Wu, W, Wang, J, Li, Y, Choi, JE, Park, KH, Sung, SW, Liu, L, Kang, CH, Wang, WC, Xu, J, Guan, P, Tan, W, Yu, CJ, Yang, G, Sihoe, ADL, Chen, Y, Choi, YY, Kim, JS, Yoon, HI, Park, IK, Xu, P, He, Q, Wang, CL, Hung, HH, Vermeulen, RCH, Cheng, I, Wu, J, Lim, WY, Tsai, FY, Chan, JKC, Li, J, Chen, H, Lin, HC, Jin, L, Liu, J, Sawada, N, Yamaji, T, Wyatt, K, Li, SA, Ma, H, Zhu, M, Wang, Z, Cheng, S, Li, X, Ren, Y, Chao, A, Iwasaki, M, Zhu, J, Jiang, G, Fei, K, Wu, G, Chen, CY, Chen, CJ, Yang, PC, Yu, J, Stevens, VL, Fraumeni, JF, Chatterjee, N, Gorlova, OY, Hsiung, CA, Amos, CI, Shen, H, Chanock, SJ, Rothman, N, Kohno, T & Lan, Q 2023, 'Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population', Nature communications, vol. 14, no. 1, 3043. https://doi.org/10.1038/s41467-023-38196-z

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title = "Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population",

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.",

author = "Jianxin Shi and Kouya Shiraishi and Jiyeon Choi and Keitaro Matsuo and Chen, {Tzu Yu} and Juncheng Dai and Hung, {Rayjean J.} and Kexin Chen and Shu, {Xiao Ou} and Kim, {Young Tae} and Landi, {Maria Teresa} and Dongxin Lin and Wei Zheng and Zhihua Yin and Baosen Zhou and Bao Song and Jiucun Wang and Seow, {Wei Jie} and Lei Song and Chang, {I. Shou} and Wei Hu and Chien, {Li Hsin} and Qiuyin Cai and Hong, {Yun Chul} and Kim, {Hee Nam} and Wu, {Yi Long} and Wong, {Maria Pik} and Richardson, {Brian Douglas} and Funderburk, {Karen M.} and Shilan Li and Tongwu Zhang and Charles Breeze and Zhaoming Wang and Batel Blechter and Bassig, {Bryan A.} and Kim, {Jin Hee} and Demetrius Albanes and Wong, {Jason Y.Y.} and Shin, {Min Ho} and Chung, {Lap Ping} and Yang Yang and An, {She Juan} and Hong Zheng and Yasushi Yatabe and Zhang, {Xu Chao} and Kim, {Young Chul} and Caporaso, {Neil E.} and Jiang Chang and Ho, {James Chung Man} and Michiaki Kubo and Yataro Daigo and Minsun Song and Yukihide Momozawa and Yoichiro Kamatani and Masashi Kobayashi and Kenichi Okubo and Takayuki Honda and Hosgood, {Dean H.} and Hideo Kunitoh and Harsh Patel and Watanabe, {Shun ichi} and Yohei Miyagi and Haruhiko Nakayama and Shingo Matsumoto and Hidehito Horinouchi and Masahiro Tsuboi and Ryuji Hamamoto and Koichi Goto and Yuichiro Ohe and Atsushi Takahashi and Akiteru Goto and Yoshihiro Minamiya and Megumi Hara and Yuichiro Nishida and Kenji Takeuchi and Kenji Wakai and Koichi Matsuda and Yoshinori Murakami and Kimihiro Shimizu and Hiroyuki Suzuki and Motonobu Saito and Yoichi Ohtaki and Kazumi Tanaka and Tangchun Wu and Fusheng Wei and Hongji Dai and Machiela, {Mitchell J.} and Jian Su and Kim, {Yeul Hong} and Oh, {In Jae} and Lee, {Victor Ho Fun} and Chang, {Gee Chen} and Tsai, {Ying Huang} and Chen, {Kuan Yu} and Huang, {Ming Shyan} and Su, {Wu Chou} and Chen, {Yuh Min} and Adeline Seow and Park, {Jae Yong} and Kweon, {Sun Seog} and Chen, {Kun Chieh} and Gao, {Yu Tang} and Biyun Qian and Chen Wu and Daru Lu and Jianjun Liu and Schwartz, {Ann G.} and Richard Houlston and Spitz, {Margaret R.} and Gorlov, {Ivan P.} and Xifeng Wu and Ping Yang and Stephen Lam and Adonina Tardon and Chu Chen and Bojesen, {Stig E.} and Mattias Johansson and Angela Risch and Heike Bickeb{\"o}ller and Ji, {Bu Tian} and Wichmann, {H. Erich} and Christiani, {David C.} and Gadi Rennert and Susanne Arnold and Paul Brennan and James McKay and Field, {John K.} and Shete, {Sanjay S.} and {Le Marchand}, Loic and Geoffrey Liu and Angeline Andrew and Kiemeney, {Lambertus A.} and Shan Zienolddiny-Narui and Kjell Grankvist and Mikael Johansson and Angela Cox and Fiona Taylor and Yuan, {Jian Min} and Philip Lazarus and Schabath, {Matthew B.} and Aldrich, {Melinda C.} and Jeon, {Hyo Sung} and Jiang, {Shih Sheng} and Sung, {Jae Sook} and Chen, {Chung Hsing} and Hsiao, {Chin Fu} and Jung, {Yoo Jin} and Huan Guo and Zhibin Hu and Laurie Burdett and Meredith Yeager and Amy Hutchinson and Belynda Hicks and Jia Liu and Bin Zhu and Berndt, {Sonja I.} and Wei Wu and Junwen Wang and Yuqing Li and Choi, {Jin Eun} and Park, {Kyong Hwa} and Sung, {Sook Whan} and Li Liu and Kang, {Chang Hyun} and Wang, {Wen Chang} and Jun Xu and Peng Guan and Wen Tan and Yu, {Chong Jen} and Gong Yang and Sihoe, {Alan Dart Loon} and Ying Chen and Choi, {Yi Young} and Kim, {Jun Suk} and Yoon, {Ho Il} and Park, {In Kyu} and Ping Xu and Qincheng He and Wang, {Chih Liang} and Hung, {Hsiao Han} and Vermeulen, {Roel C.H.} and Iona Cheng and Junjie Wu and Lim, {Wei Yen} and Tsai, {Fang Yu} and Chan, {John K.C.} and Jihua Li and Hongyan Chen and Lin, {Hsien Chih} and Li Jin and Jie Liu and Norie Sawada and Taiki Yamaji and Kathleen Wyatt and Li, {Shengchao A.} and Hongxia Ma and Meng Zhu and Zhehai Wang and Sensen Cheng and Xuelian Li and Yangwu Ren and Ann Chao and Motoki Iwasaki and Junjie Zhu and Gening Jiang and Ke Fei and Guoping Wu and Chen, {Chih Yi} and Chen, {Chien Jen} and Yang, {Pan Chyr} and Jinming Yu and Stevens, {Victoria L.} and Fraumeni, {Joseph F.} and Nilanjan Chatterjee and Gorlova, {Olga Y.} and Hsiung, {Chao Agnes} and Amos, {Christopher I.} and Hongbing Shen and Chanock, {Stephen J.} and Nathaniel Rothman and Takashi Kohno and Qing Lan",

note = "Publisher Copyright: {\textcopyright} 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-38196-z",

language = "English (US)",

volume = "14",

journal = "Nature communications",

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TY - JOUR

T1 - Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

AU - Shi, Jianxin

AU - Shiraishi, Kouya

AU - Choi, Jiyeon

AU - Matsuo, Keitaro

AU - Chen, Tzu Yu

AU - Dai, Juncheng

AU - Hung, Rayjean J.

AU - Chen, Kexin

AU - Shu, Xiao Ou

AU - Kim, Young Tae

AU - Landi, Maria Teresa

AU - Lin, Dongxin

AU - Zheng, Wei

AU - Yin, Zhihua

AU - Zhou, Baosen

AU - Song, Bao

AU - Wang, Jiucun

AU - Seow, Wei Jie

AU - Song, Lei

AU - Chang, I. Shou

AU - Hu, Wei

AU - Chien, Li Hsin

AU - Cai, Qiuyin

AU - Hong, Yun Chul

AU - Kim, Hee Nam

AU - Wu, Yi Long

AU - Wong, Maria Pik

AU - Richardson, Brian Douglas

AU - Funderburk, Karen M.

AU - Li, Shilan

AU - Zhang, Tongwu

AU - Breeze, Charles

AU - Wang, Zhaoming

AU - Blechter, Batel

AU - Bassig, Bryan A.

AU - Kim, Jin Hee

AU - Albanes, Demetrius

AU - Wong, Jason Y.Y.

AU - Shin, Min Ho

AU - Chung, Lap Ping

AU - Yang, Yang

AU - An, She Juan

AU - Zheng, Hong

AU - Yatabe, Yasushi

AU - Zhang, Xu Chao

AU - Kim, Young Chul

AU - Caporaso, Neil E.

AU - Chang, Jiang

AU - Ho, James Chung Man

AU - Kubo, Michiaki

AU - Daigo, Yataro

AU - Song, Minsun

AU - Momozawa, Yukihide

AU - Kamatani, Yoichiro

AU - Kobayashi, Masashi

AU - Okubo, Kenichi

AU - Honda, Takayuki

AU - Hosgood, Dean H.

AU - Kunitoh, Hideo

AU - Patel, Harsh

AU - Watanabe, Shun ichi

AU - Miyagi, Yohei

AU - Nakayama, Haruhiko

AU - Matsumoto, Shingo

AU - Horinouchi, Hidehito

AU - Tsuboi, Masahiro

AU - Hamamoto, Ryuji

AU - Goto, Koichi

AU - Ohe, Yuichiro

AU - Takahashi, Atsushi

AU - Goto, Akiteru

AU - Minamiya, Yoshihiro

AU - Hara, Megumi

AU - Nishida, Yuichiro

AU - Takeuchi, Kenji

AU - Wakai, Kenji

AU - Matsuda, Koichi

AU - Murakami, Yoshinori

AU - Shimizu, Kimihiro

AU - Suzuki, Hiroyuki

AU - Saito, Motonobu

AU - Ohtaki, Yoichi

AU - Tanaka, Kazumi

AU - Wu, Tangchun

AU - Wei, Fusheng

AU - Dai, Hongji

AU - Machiela, Mitchell J.

AU - Su, Jian

AU - Kim, Yeul Hong

AU - Oh, In Jae

AU - Lee, Victor Ho Fun

AU - Chang, Gee Chen

AU - Tsai, Ying Huang

AU - Chen, Kuan Yu

AU - Huang, Ming Shyan

AU - Su, Wu Chou

AU - Chen, Yuh Min

AU - Seow, Adeline

AU - Park, Jae Yong

AU - Kweon, Sun Seog

AU - Chen, Kun Chieh

AU - Gao, Yu Tang

AU - Qian, Biyun

AU - Wu, Chen

AU - Lu, Daru

AU - Liu, Jianjun

AU - Schwartz, Ann G.

AU - Houlston, Richard

AU - Spitz, Margaret R.

AU - Gorlov, Ivan P.

AU - Wu, Xifeng

AU - Yang, Ping

AU - Lam, Stephen

AU - Tardon, Adonina

AU - Chen, Chu

AU - Bojesen, Stig E.

AU - Johansson, Mattias

AU - Risch, Angela

AU - Bickeböller, Heike

AU - Ji, Bu Tian

AU - Wichmann, H. Erich

AU - Christiani, David C.

AU - Rennert, Gadi

AU - Arnold, Susanne

AU - Brennan, Paul

AU - McKay, James

AU - Field, John K.

AU - Shete, Sanjay S.

AU - Le Marchand, Loic

AU - Liu, Geoffrey

AU - Andrew, Angeline

AU - Kiemeney, Lambertus A.

AU - Zienolddiny-Narui, Shan

AU - Grankvist, Kjell

AU - Johansson, Mikael

AU - Cox, Angela

AU - Taylor, Fiona

AU - Yuan, Jian Min

AU - Lazarus, Philip

AU - Schabath, Matthew B.

AU - Aldrich, Melinda C.

AU - Jeon, Hyo Sung

AU - Jiang, Shih Sheng

AU - Sung, Jae Sook

AU - Chen, Chung Hsing

AU - Hsiao, Chin Fu

AU - Jung, Yoo Jin

AU - Guo, Huan

AU - Hu, Zhibin

AU - Burdett, Laurie

AU - Yeager, Meredith

AU - Hutchinson, Amy

AU - Hicks, Belynda

AU - Liu, Jia

AU - Zhu, Bin

AU - Berndt, Sonja I.

AU - Wu, Wei

AU - Wang, Junwen

AU - Li, Yuqing

AU - Choi, Jin Eun

AU - Park, Kyong Hwa

AU - Sung, Sook Whan

AU - Liu, Li

AU - Kang, Chang Hyun

AU - Wang, Wen Chang

AU - Xu, Jun

AU - Guan, Peng

AU - Tan, Wen

AU - Yu, Chong Jen

AU - Yang, Gong

AU - Sihoe, Alan Dart Loon

AU - Chen, Ying

AU - Choi, Yi Young

AU - Kim, Jun Suk

AU - Yoon, Ho Il

AU - Park, In Kyu

AU - Xu, Ping

AU - He, Qincheng

AU - Wang, Chih Liang

AU - Hung, Hsiao Han

AU - Vermeulen, Roel C.H.

AU - Cheng, Iona

AU - Wu, Junjie

AU - Lim, Wei Yen

AU - Tsai, Fang Yu

AU - Chan, John K.C.

AU - Li, Jihua

AU - Chen, Hongyan

AU - Lin, Hsien Chih

AU - Jin, Li

AU - Liu, Jie

AU - Sawada, Norie

AU - Yamaji, Taiki

AU - Wyatt, Kathleen

AU - Li, Shengchao A.

AU - Ma, Hongxia

AU - Zhu, Meng

AU - Wang, Zhehai

AU - Cheng, Sensen

AU - Li, Xuelian

AU - Ren, Yangwu

AU - Chao, Ann

AU - Iwasaki, Motoki

AU - Zhu, Junjie

AU - Jiang, Gening

AU - Fei, Ke

AU - Wu, Guoping

AU - Chen, Chih Yi

AU - Chen, Chien Jen

AU - Yang, Pan Chyr

AU - Yu, Jinming

AU - Stevens, Victoria L.

AU - Fraumeni, Joseph F.

AU - Chatterjee, Nilanjan

AU - Gorlova, Olga Y.

AU - Hsiung, Chao Agnes

AU - Amos, Christopher I.

AU - Shen, Hongbing

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

AU - Kohno, Takashi

AU - Lan, Qing

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85160220141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85160220141&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-38196-z

DO - 10.1038/s41467-023-38196-z

M3 - Article

C2 - 37236969

AN - SCOPUS:85160220141

SN - 2041-1723

VL - 14

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3043

ER -

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

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UN SDGs

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