Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population
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Published:2023-05-26
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Shi JianxinORCID, Shiraishi KouyaORCID, Choi JiyeonORCID, Matsuo Keitaro, Chen Tzu-YuORCID, Dai JunchengORCID, Hung Rayjean J.ORCID, Chen Kexin, Shu Xiao-Ou, Kim Young TaeORCID, Landi Maria Teresa, Lin Dongxin, Zheng WeiORCID, Yin Zhihua, Zhou BaosenORCID, Song Bao, Wang JiucunORCID, Seow Wei Jie, Song Lei, Chang I-ShouORCID, Hu Wei, Chien Li-Hsin, Cai QiuyinORCID, Hong Yun-Chul, Kim Hee Nam, Wu Yi-LongORCID, Wong Maria Pik, Richardson Brian Douglas, Funderburk Karen M., Li Shilan, Zhang TongwuORCID, Breeze Charles, Wang ZhaomingORCID, Blechter Batel, Bassig Bryan A., Kim Jin Hee, Albanes DemetriusORCID, Wong Jason Y. Y., Shin Min-HoORCID, Chung Lap Ping, Yang Yang, An She-Juan, Zheng Hong, Yatabe Yasushi, Zhang Xu-ChaoORCID, Kim Young-Chul, Caporaso Neil E., Chang Jiang, Ho James Chung ManORCID, Kubo MichiakiORCID, Daigo Yataro, Song Minsun, Momozawa Yukihide, Kamatani YoichiroORCID, Kobayashi Masashi, Okubo Kenichi, Honda Takayuki, Hosgood Dean H., Kunitoh Hideo, Patel HarshORCID, Watanabe Shun-ichi, Miyagi YoheiORCID, Nakayama Haruhiko, Matsumoto Shingo, Horinouchi HidehitoORCID, Tsuboi Masahiro, Hamamoto RyujiORCID, Goto KoichiORCID, Ohe Yuichiro, Takahashi AtsushiORCID, Goto Akiteru, Minamiya Yoshihiro, Hara MegumiORCID, Nishida YuichiroORCID, Takeuchi Kenji, Wakai Kenji, Matsuda KoichiORCID, Murakami YoshinoriORCID, Shimizu KimihiroORCID, Suzuki Hiroyuki, Saito MotonobuORCID, Ohtaki YoichiORCID, Tanaka Kazumi, Wu TangchunORCID, Wei Fusheng, Dai Hongji, Machiela Mitchell J.ORCID, Su Jian, Kim Yeul HongORCID, Oh In-JaeORCID, Lee Victor Ho FunORCID, 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 JianjunORCID, Schwartz Ann G., Houlston RichardORCID, Spitz Margaret R., Gorlov Ivan P., Wu XifengORCID, Yang Ping, Lam Stephen, Tardon AdoninaORCID, Chen Chu, Bojesen Stig E.ORCID, Johansson MattiasORCID, Risch AngelaORCID, Bickeböller HeikeORCID, Ji Bu-Tian, Wichmann H-Erich, Christiani David C.ORCID, Rennert GadiORCID, Arnold SusanneORCID, Brennan Paul, McKay James, Field John K.ORCID, Shete Sanjay S.ORCID, Le Marchand Loic, Liu Geoffrey, Andrew Angeline, Kiemeney Lambertus A.ORCID, Zienolddiny-Narui Shan, Grankvist KjellORCID, Johansson MikaelORCID, Cox AngelaORCID, Taylor Fiona, Yuan Jian-MinORCID, Lazarus Philip, Schabath Matthew B.ORCID, Aldrich Melinda C., Jeon Hyo-Sung, Jiang Shih Sheng, Sung Jae Sook, Chen Chung-HsingORCID, Hsiao Chin-Fu, Jung Yoo Jin, Guo Huan, Hu ZhibinORCID, Burdett Laurie, Yeager Meredith, Hutchinson Amy, Hicks BelyndaORCID, 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-JenORCID, 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-HanORCID, Vermeulen Roel C. H., Cheng Iona, Wu Junjie, Lim Wei-Yen, Tsai Fang-Yu, Chan John K. C.ORCID, Li Jihua, Chen Hongyan, Lin Hsien-Chih, Jin Li, Liu Jie, Sawada NorieORCID, Yamaji Taiki, Wyatt Kathleen, Li Shengchao A.ORCID, 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-ChyrORCID, Yu Jinming, Stevens Victoria L.ORCID, Fraumeni Joseph F., Chatterjee Nilanjan, Gorlova Olga Y., Hsiung Chao AgnesORCID, Amos Christopher I.ORCID, Shen HongbingORCID, Chanock Stephen J., Rothman Nathaniel, Kohno TakashiORCID, Lan QingORCID
Abstract
AbstractLung 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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