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.

Metadata

Item Type:	Article
Authors/Creators:	Shi, J. https://orcid.org/0000-0001-8606-4707 Shiraishi, K. https://orcid.org/0000-0002-5821-7400 Choi, J. https://orcid.org/0000-0002-0955-2384 Matsuo, K. Chen, T.-Y. https://orcid.org/0000-0002-0146-3782 Dai, J. https://orcid.org/0000-0002-3909-5671 Hung, R.J. https://orcid.org/0000-0002-4486-7496 Chen, K. Shu, X.-O. Kim, Y.T. https://orcid.org/0000-0001-9006-4881 Landi, M.T. Lin, D. Zheng, W. https://orcid.org/0000-0003-1226-070X Yin, Z. Zhou, B. https://orcid.org/0000-0002-5311-3880 Song, B. Wang, J. https://orcid.org/0000-0003-2765-0620 Seow, W.J. Song, L. Chang, I.-S. https://orcid.org/0000-0002-6254-8114 Hu, W. Chien, L.-H. Cai, Q. https://orcid.org/0000-0002-9384-5648 Hong, Y.-C. Kim, H.N. Wu, Y.-L. https://orcid.org/0000-0002-3611-0258 Wong, M.P. Richardson, B.D. Funderburk, K.M. Li, S. Zhang, T. https://orcid.org/0000-0003-2124-2706 Breeze, C. Wang, Z. https://orcid.org/0000-0001-7556-3869 Blechter, B. Bassig, B.A. Kim, J.H. Albanes, D. https://orcid.org/0000-0001-8330-4293 Wong, J.Y.Y. Shin, M.-H. https://orcid.org/0000-0002-2217-5624 Chung, L.P. Yang, Y. An, S.-J. Zheng, H. Yatabe, Y. Zhang, X.-C. https://orcid.org/0000-0002-4138-8115 Kim, Y.-C. Caporaso, N.E. Chang, J. Ho, J.C.M. https://orcid.org/0000-0003-4499-5284 Kubo, M. https://orcid.org/0000-0002-0095-2322 Daigo, Y. Song, M. Momozawa, Y. Kamatani, Y. https://orcid.org/0000-0001-8748-5597 Kobayashi, M. Okubo, K. Honda, T. Hosgood, D.H. Kunitoh, H. Patel, H. https://orcid.org/0000-0002-9860-8254 Watanabe, S.-I. Miyagi, Y. https://orcid.org/0000-0002-0056-7010 Nakayama, H. Matsumoto, S. Horinouchi, H. https://orcid.org/0000-0001-9090-801X Tsuboi, M. Hamamoto, R. https://orcid.org/0000-0002-2632-1334 Goto, K. https://orcid.org/0000-0002-3023-2510 Ohe, Y. Takahashi, A. https://orcid.org/0000-0001-7099-8767 Goto, A. Minamiya, Y. Hara, M. https://orcid.org/0000-0002-8708-3237 Nishida, Y. https://orcid.org/0000-0003-2320-7234 Takeuchi, K. Wakai, K. Matsuda, K. https://orcid.org/0000-0001-7292-2686 Murakami, Y. https://orcid.org/0000-0002-2826-4396 Shimizu, K. https://orcid.org/0000-0003-4076-5174 Suzuki, H. Saito, M. https://orcid.org/0000-0001-5072-3520 Ohtaki, Y. https://orcid.org/0000-0001-5485-3234 Tanaka, K. Wu, T. https://orcid.org/0000-0001-9931-5106 Wei, F. Dai, H. Machiela, M.J. https://orcid.org/0000-0001-6538-9705 Su, J. Kim, Y.H. https://orcid.org/0000-0002-2555-2333 Oh, I.-J. https://orcid.org/0000-0003-4837-1321 Lee, V.H.F. https://orcid.org/0000-0002-6283-978X Chang, G.-C. Tsai, Y.-H. Chen, K.-Y. Huang, M.-S. Su, W.-C. Chen, Y.-M. Seow, A. Park, J.Y. Kweon, S.-S. Chen, K.-C. Gao, Y.-T. Qian, B. Wu, C. Lu, D. Liu, J. https://orcid.org/0000-0002-3255-3019 Schwartz, A.G. Houlston, R. https://orcid.org/0000-0002-5268-0242 Spitz, M.R. Gorlov, I.P. Wu, X. https://orcid.org/0000-0003-2980-8129 Yang, P. Lam, S. Tardon, A. https://orcid.org/0000-0001-5150-1209 Chen, C. Bojesen, S.E. https://orcid.org/0000-0002-4061-4133 Johansson, M. https://orcid.org/0000-0002-3116-5081 Risch, A. https://orcid.org/0000-0002-8026-5505 Bickeböller, H. https://orcid.org/0000-0002-3361-5488 Ji, B.-T. Wichmann, H.-E. Christiani, D.C. https://orcid.org/0000-0002-0301-0242 Rennert, G. https://orcid.org/0000-0002-8512-068X Arnold, S. https://orcid.org/0000-0001-6542-9551 Brennan, P. McKay, J. Field, J.K. https://orcid.org/0000-0003-3951-6365 Shete, S.S. https://orcid.org/0000-0001-7622-376X Le Marchand, L. Liu, G. Andrew, A. Kiemeney, L.A. https://orcid.org/0000-0002-2368-1326 Zienolddiny-Narui, S. Grankvist, K. https://orcid.org/0000-0003-4289-2097 Johansson, M. https://orcid.org/0000-0003-4182-8923 Cox, A. https://orcid.org/0000-0002-5138-1099 Taylor, F. Yuan, J.-M. https://orcid.org/0000-0002-4620-3108 Lazarus, P. Schabath, M.B. https://orcid.org/0000-0003-3241-3216 Aldrich, M.C. Jeon, H.-S. Jiang, S.S. Sung, J.S. Chen, C.-H. https://orcid.org/0000-0002-1205-7368 Hsiao, C.-F. Jung, Y.J. Guo, H. Hu, Z. https://orcid.org/0000-0002-8277-5234 Burdett, L. Yeager, M. Hutchinson, A. Hicks, B. https://orcid.org/0000-0001-8014-4888 Liu, J. Zhu, B. Berndt, S.I. Wu, W. Wang, J. Li, Y. Choi, J.E. Park, K.H. Sung, S.W. Liu, L. Kang, C.H. Wang, W.-C. Xu, J. Guan, P. Tan, W. Yu, C.-J. https://orcid.org/0000-0001-5664-9392 Yang, G. Sihoe, A.D.L. Chen, Y. Choi, Y.Y. Kim, J.S. Yoon, H.-I. Park, I.K. Xu, P. He, Q. Wang, C.-L. Hung, H.-H. https://orcid.org/0000-0002-5466-4828 Vermeulen, R.C.H. Cheng, I. Wu, J. Lim, W.-Y. Tsai, F.-Y. Chan, J.K.C. https://orcid.org/0000-0001-5068-6707 Li, J. Chen, H. Lin, H.-C. Jin, L. Liu, J. Sawada, N. https://orcid.org/0000-0002-9936-1476 Yamaji, T. Wyatt, K. Li, S.A. https://orcid.org/0000-0001-9252-1492 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, C.-Y. Chen, C.-J. Yang, P.-C. https://orcid.org/0000-0001-6330-6048 Yu, J. Stevens, V.L. https://orcid.org/0000-0003-0259-4407 Fraumeni, J.F. Chatterjee, N. Gorlova, O.Y. Hsiung, C.A. https://orcid.org/0000-0003-1427-6641 Amos, C.I. https://orcid.org/0000-0002-8540-7023 Shen, H. https://orcid.org/0000-0002-2581-5906 Chanock, S.J. Rothman, N. Kohno, T. https://orcid.org/0000-0002-5371-706X Lan, Q. https://orcid.org/0000-0002-0888-8839
Copyright, Publisher and Additional Information:	Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023
Keywords:	Humans; Lung Neoplasms; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Adenocarcinoma of Lung; Asia, Eastern
Dates:	Published: 26 May 2023 Published (online): 26 May 2023 Accepted: 19 April 2023
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Oncology (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	05 Jun 2023 12:11
Last Modified:	13 Jun 2023 12:30
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1038/s41467-023-38196-z
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:199749

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

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