Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.
Date
2023-05-26ICR Author
Author
Shi, J
Shiraishi, K
Choi, J
Matsuo, K
Chen, T-Y
Dai, J
Hung, RJ
Chen, K
Shu, X-O
Kim, YT
Landi, MT
Lin, D
Zheng, W
Yin, Z
Zhou, B
Song, B
Wang, J
Seow, WJ
Song, L
Chang, I-S
Hu, W
Chien, L-H
Cai, Q
Hong, Y-C
Kim, HN
Wu, Y-L
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, M-H
Chung, LP
Yang, Y
An, S-J
Zheng, H
Yatabe, Y
Zhang, X-C
Kim, Y-C
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, S-I
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, I-J
Lee, VHF
Chang, G-C
Tsai, Y-H
Chen, K-Y
Huang, M-S
Su, W-C
Chen, Y-M
Seow, A
Park, JY
Kweon, S-S
Chen, K-C
Gao, Y-T
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, B-T
Wichmann, H-E
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, J-M
Lazarus, P
Schabath, MB
Aldrich, MC
Jeon, H-S
Jiang, SS
Sung, JS
Chen, C-H
Hsiao, C-F
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, W-C
Xu, J
Guan, P
Tan, W
Yu, C-J
Yang, G
Sihoe, ADL
Chen, Y
Choi, YY
Kim, JS
Yoon, H-I
Park, IK
Xu, P
He, Q
Wang, C-L
Hung, H-H
Vermeulen, RCH
Cheng, I
Wu, J
Lim, W-Y
Tsai, F-Y
Chan, JKC
Li, J
Chen, H
Lin, H-C
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, C-Y
Chen, C-J
Yang, P-C
Yu, J
Stevens, VL
Fraumeni, JF
Chatterjee, N
Gorlova, OY
Hsiung, CA
Amos, CI
Shen, H
Chanock, SJ
Rothman, N
Kohno, T
Lan, Q
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Genome-Wide Association Study
Genetic Predisposition to Disease
Adenocarcinoma of Lung
Asia, Eastern
Lung Neoplasms
Polymorphism, Single Nucleotide
Research team
Cancer Genomics
Language
eng
Date accepted
2023-04-19
License start date
2023-05-26
Citation
Nature Communications, 2023, 14 (1), pp. 3043 -
Publisher
NATURE PORTFOLIO