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 |
|---|---|
| Article number | 3043 |
| Pages (from-to) | 3043 |
| Journal | NATURE COMMUNICATIONS |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 26 May 2023 |
Bibliographical note
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.Keywords
- Humans
- Genome-Wide Association Study
- Genetic Predisposition to Disease
- Adenocarcinoma of Lung/genetics
- Asia, Eastern/epidemiology
- Lung Neoplasms/epidemiology
- Polymorphism, Single Nucleotide
Fields of Science and Technology Classification 2012
- 305 Other Human Medicine, Health Sciences
- 301 Medical-Theoretical Sciences, Pharmacy
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In: NATURE COMMUNICATIONS, Vol. 14, No. 1, 3043, 26.05.2023, p. 3043.
Research output: Contribution to journal › Article › peer-review
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
N1 - © 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2023/5/26
Y1 - 2023/5/26
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 (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.
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 (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.
KW - Humans
KW - Genome-Wide Association Study
KW - Genetic Predisposition to Disease
KW - Adenocarcinoma of Lung/genetics
KW - Asia, Eastern/epidemiology
KW - Lung Neoplasms/epidemiology
KW - Polymorphism, Single Nucleotide
UR - http://www.scopus.com/inward/record.url?scp=85160220141&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-38196-z
DO - 10.1038/s41467-023-38196-z
M3 - Article
C2 - 37236969
SN - 2041-1723
VL - 14
SP - 3043
JO - NATURE COMMUNICATIONS
JF - NATURE COMMUNICATIONS
IS - 1
M1 - 3043
ER -