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; 5...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38196-z |
| _version_ | 1797817852958343168 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jianxin Shi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T09:00:38Z |
| format | Article |
| id | doaj.art-91497ad90e1e4c55a94f6aaf69b16ba4 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T09:00:38Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-91497ad90e1e4c55a94f6aaf69b16ba42023-05-28T11:22:33ZengNature PortfolioNature Communications2041-17232023-05-0114111710.1038/s41467-023-38196-zGenome-wide association study of lung adenocarcinoma in East Asia and comparison with a European populationJianxin Shi0Kouya Shiraishi1Jiyeon Choi2Keitaro Matsuo3Tzu-Yu Chen4Juncheng Dai5Rayjean J. Hung6Kexin Chen7Xiao-Ou Shu8Young Tae Kim9Maria Teresa Landi10Dongxin Lin11Wei Zheng12Zhihua Yin13Baosen Zhou14Bao Song15Jiucun Wang16Wei Jie Seow17Lei Song18I-Shou Chang19Wei Hu20Li-Hsin Chien21Qiuyin Cai22Yun-Chul Hong23Hee Nam Kim24Yi-Long Wu25Maria Pik Wong26Brian Douglas Richardson27Karen M. Funderburk28Shilan Li29Tongwu Zhang30Charles Breeze31Zhaoming Wang32Batel Blechter33Bryan A. Bassig34Jin Hee Kim35Demetrius Albanes36Jason Y. Y. Wong37Min-Ho Shin38Lap Ping Chung39Yang Yang40She-Juan An41Hong Zheng42Yasushi Yatabe43Xu-Chao Zhang44Young-Chul Kim45Neil E. Caporaso46Jiang Chang47James Chung Man Ho48Michiaki Kubo49Yataro Daigo50Minsun Song51Yukihide Momozawa52Yoichiro Kamatani53Masashi Kobayashi54Kenichi Okubo55Takayuki Honda56Dean H. Hosgood57Hideo Kunitoh58Harsh Patel59Shun-ichi Watanabe60Yohei Miyagi61Haruhiko Nakayama62Shingo Matsumoto63Hidehito Horinouchi64Masahiro Tsuboi65Ryuji Hamamoto66Koichi Goto67Yuichiro Ohe68Atsushi Takahashi69Akiteru Goto70Yoshihiro Minamiya71Megumi Hara72Yuichiro Nishida73Kenji Takeuchi74Kenji Wakai75Koichi Matsuda76Yoshinori Murakami77Kimihiro Shimizu78Hiroyuki Suzuki79Motonobu Saito80Yoichi Ohtaki81Kazumi Tanaka82Tangchun Wu83Fusheng Wei84Hongji Dai85Mitchell J. Machiela86Jian Su87Yeul Hong Kim88In-Jae Oh89Victor Ho Fun Lee90Gee-Chen Chang91Ying-Huang Tsai92Kuan-Yu Chen93Ming-Shyan Huang94Wu-Chou Su95Yuh-Min Chen96Adeline Seow97Jae Yong Park98Sun-Seog Kweon99Kun-Chieh Chen100Yu-Tang Gao101Biyun Qian102Chen Wu103Daru Lu104Jianjun Liu105Ann G. Schwartz106Richard Houlston107Margaret R. Spitz108Ivan P. Gorlov109Xifeng Wu110Ping Yang111Stephen Lam112Adonina Tardon113Chu Chen114Stig E. Bojesen115Mattias Johansson116Angela Risch117Heike Bickeböller118Bu-Tian Ji119H-Erich Wichmann120David C. Christiani121Gadi Rennert122Susanne Arnold123Paul Brennan124James McKay125John K. Field126Sanjay S. Shete127Loic Le Marchand128Geoffrey Liu129Angeline Andrew130Lambertus A. Kiemeney131Shan Zienolddiny-Narui132Kjell Grankvist133Mikael Johansson134Angela Cox135Fiona Taylor136Jian-Min Yuan137Philip Lazarus138Matthew B. Schabath139Melinda C. Aldrich140Hyo-Sung Jeon141Shih Sheng Jiang142Jae Sook Sung143Chung-Hsing Chen144Chin-Fu Hsiao145Yoo Jin Jung146Huan Guo147Zhibin Hu148Laurie Burdett149Meredith Yeager150Amy Hutchinson151Belynda Hicks152Jia Liu153Bin Zhu154Sonja I. Berndt155Wei Wu156Junwen Wang157Yuqing Li158Jin Eun Choi159Kyong Hwa Park160Sook Whan Sung161Li Liu162Chang Hyun Kang163Wen-Chang Wang164Jun Xu165Peng Guan166Wen Tan167Chong-Jen Yu168Gong Yang169Alan Dart Loon Sihoe170Ying Chen171Yi Young Choi172Jun Suk Kim173Ho-Il Yoon174In Kyu Park175Ping Xu176Qincheng He177Chih-Liang Wang178Hsiao-Han Hung179Roel C. H. Vermeulen180Iona Cheng181Junjie Wu182Wei-Yen Lim183Fang-Yu Tsai184John K. C. Chan185Jihua Li186Hongyan Chen187Hsien-Chih Lin188Li Jin189Jie Liu190Norie Sawada191Taiki Yamaji192Kathleen Wyatt193Shengchao A. Li194Hongxia Ma195Meng Zhu196Zhehai Wang197Sensen Cheng198Xuelian Li199Yangwu Ren200Ann Chao201Motoki Iwasaki202Junjie Zhu203Gening Jiang204Ke Fei205Guoping Wu206Chih-Yi Chen207Chien-Jen Chen208Pan-Chyr Yang209Jinming Yu210Victoria L. Stevens211Joseph F. Fraumeni212Nilanjan Chatterjee213Olga Y. Gorlova214Chao Agnes Hsiung215Christopher I. Amos216Hongbing Shen217Stephen J. Chanock218Nathaniel Rothman219Takashi Kohno220Qing Lan221Division of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Genome Biology, National Cancer Research InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Prevention, Aichi Cancer Center Research InstituteInstitute of Population Health Sciences, National Health Research InstitutesDepartment of Epidemiology, School of Public Health, Nanjing Medical UniversityProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai HealthDepartment of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer CenterCancer Research Institute, Seoul National University College of MedicineDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer CenterDepartment of Epidemiology, School of Public Health, China Medical UniversityDepartment of Clinical Epidemiology and Center of Evidence Based Medicine, The First Hospital of China Medical UniversityDepartment of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical SciencesMinistry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan UniversityDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteNational Institute of Cancer Research, National Health Research InstitutesDivision of Cancer Epidemiology and Genetics, National Cancer InstituteInstitute of Population Health Sciences, National Health Research InstitutesDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer CenterDepartment of Preventive Medicine, Seoul National University College of MedicineDepartment of Preventive Medicine, Chonnam National University Medical SchoolGuangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Pathology, Queen Mary HospitalDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Computational Biology, St. Jude Children’s Research HospitalDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Environmental Health, Graduate School of Public Health, Seoul National UniversityDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Preventive Medicine, Chonnam National University Medical SchoolDepartment of Pathology, Queen Mary HospitalShanghai Pulmonary HospitalGuangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityDepartment of Pathology and Clinical Laboratories, National Cancer Center HospitalGuangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesLung and Esophageal Cancer Clinic, Chonnam National University Hwasun HospitalDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Medicine, The University of Hong Kong, Queen Mary HospitalLaboratory for Genotyping Development, RIKEN Center for Integrative Medical SciencesCenter for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of TokyoDepartment of Statistics & Research Institute of Natural Sciences, Sookmyung Women’s UniversityLaboratory for Genotyping Development, RIKEN Center for Integrative Medical SciencesLaboratory for Statistical Analysis, RIKEN Center for Integrative Medical SciencesDepartment of Thoracic Surgery, Tokyo Medical and Dental UniversityDepartment of Thoracic Surgery, Tokyo Medical and Dental UniversityDepartment of Respiratory Medicine, Tokyo Medical and Dental UniversityDepartment of Epidemiology and Population Health, Albert Einstein College of MedicineDepartment of Medical Oncology, Japanese Red Cross Medical CenterDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Thoracic Surgery, National Cancer Center HospitalMolecular Pathology and Genetics Division, Kanagawa Cancer Center Research InstituteDepartment of Thoracic Surgery, Kanagawa Cancer CenterDepartment of Thoracic Oncology, National Cancer Center Hospital EastDepartment of Thoracic Surgery, National Cancer Center HospitalDepartment of Thoracic Surgery, National Cancer Center Hospital EastDivision of Medical AI Research and Development, National Cancer Center Research InstituteDepartment of Thoracic Oncology, National Cancer Center Hospital EastDepartment of Thoracic Surgery, National Cancer Center HospitalLaboratory for Statistical Analysis, RIKEN Center for Integrative Medical SciencesDepartment of Cellular and Organ Pathology, Graduate School of Medicine, Akita UniversityDepartment of Thoracic Surgery, Graduate School of Medicine, Akita UniversityDepartment of Preventive Medicine, Faculty of Medicine, Saga UniversityDepartment of Preventive Medicine, Faculty of Medicine, Saga UniversityDepartment of Preventive Medicine, Nagoya University Graduate School of MedicineDepartment of Preventive Medicine, Nagoya University Graduate School of MedicineLaboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Science, Graduate School of Frontier Sciences, The University of TokyoDivision of Molecular Pathology, Institute of Medical Science, The University of TokyoDepartment of Surgery, Division of General Thoracic Surgery, Shinshu University School of Medicine AsahiDepartment of Chest Surgery, Fukushima Medical University School of MedicineDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University School of MedicineDepartment of Integrative center of General Surgery, Gunma University HospitalDepartment of Integrative center of General Surgery, Gunma University HospitalInstitute of Occupational Medicine and Ministry of Education Key Lab for Environment and Health, School of Public Health, Huazhong University of Science and TechnologyChina National Environmental Monitoring CenterDepartment of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityDivision of Cancer Epidemiology and Genetics, National Cancer InstituteGuangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesDepartment of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam HospitalLung and Esophageal Cancer Clinic, Chonnam National University Hwasun HospitalDepartment of Clinical Oncology, The University of Hong Kong, Queen Mary HospitalSchool of Medicine and Institute of Medicine, Chung Shan Medical UniversityDepartment of Respiratory Therapy, Chang Gung UniversityDepartment of Internal Medicine, National Taiwan University Hospital and College of MedicineDepartment of Internal Medicine, E-Da Cancer Hospital, I-Shou University and Kaohsiung Medical UniversityDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDepartment of Chest Medicine, Taipei Veterans General Hospital, and school of Medicine, National Yang Ming Chiao Tung UniversitySaw Swee Hock School of Public Health, National University of SingaporeLung Cancer Center, Kyungpook National University Medical CenterDepartment of Preventive Medicine, Chonnam National University Medical SchoolDepartment of Internal Medicine, Division of Pulmonary Medicine, Chung Shan Medical University HospitalDepartment of Epidemiology, Shanghai Cancer InstituteDepartment of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityDepartment of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeMinistry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan UniversityGenome Institute of Singapore, Agency of Science, Technology and ResearchKarmanos Cancer InstituteDivision of Genetics and Epidemiology, Institute of Cancer ResearchDepartment of Medicine, Section of Epidemiology and Population Science, Institute for Clinical and Translational ResearchDepartment of Medicine, Section of Epidemiology and Population Science, Institute for Clinical and Translational ResearchSchool of Medicine, Zhejiang UniversityDepartment of Health Sciences Research, Mayo ClinicBritish Columbia Cancer AgencyIUOPA, University of Oviedo and CIBERESPPublic Health Sciences Division, Fred Hutchinson Cancer CenterFaculty of Health and Medical Sciences, University of CopenhagenInternational Agency for Research on Cancer (IARC/WHO)German Cancer Research Center (DKFZ)University Medical Center GoettingenDivision of Cancer Epidemiology and Genetics, National Cancer InstituteInstitute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians UniversityHarvard TH Chan School of Public HealthCarmel Medical CenterMarkey Cancer CenterInternational Agency for Research on Cancer (IARC/WHO)International Agency for Research on Cancer (IARC/WHO)Liverpool UniversityThe University of Texas MD Anderson Cancer CenterEpidemiology Program, University of Hawaii Cancer CenterPrincess Margaret Cancer CenterNorris Cotton Cancer CenterRadboud University Medical CenterNational Institute of Occupational HealthDepartment of Medical Biosciences, Umeå UniversityDepartment of Radiation Sciences, Umeå UniversityUniversity of SheffieldUniversity of SheffieldUPMC Hillman Cancer Center and Department of Epidemiology, School of Public Health, University of PittsburghWashington State University College of PharmacyDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research InstituteDepartment of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical CenterCancer Research Center, Kyungpook National University Medical CenterNational Institute of Cancer Research, National Health Research InstitutesDepartment of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam HospitalNational Institute of Cancer Research, National Health Research InstitutesInstitute of Population Health Sciences, National Health Research InstitutesDepartment of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of MedicineDepartment of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Epidemiology, School of Public Health, Nanjing Medical UniversityDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Epidemiology, School of Public Health, China Medical UniversityDepartment of Biochemistry, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong KongDepartment of Human Genetics, Genome Institute of SingaporeCancer Research Center, Kyungpook National University Medical CenterDepartment of Internal Medicine, Division of Oncology/Hematology, College of Medicine, Korea University Anam HospitalDepartment of Thoracic and Cardiovascular Surgery, Seoul National University Bundang HospitalDepartment of Oncology, Cancer Center, Union Hospital, Huazhong University of Science and TechnologyDepartment of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of MedicineThe Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical UniversitySchool of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong KongDepartment of Epidemiology, School of Public Health, China Medical UniversityDepartment of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Internal Medicine, National Taiwan University Hospital Hsin-Chu BranchDivision of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer CenterGleneagles Hong Kong HospitalSaw Swee Hock School of Public Health, National University of SingaporeCancer Research Center, Kyungpook National University Medical CenterDepartment of Internal Medicine, Division of Medical Oncology, College of Medicine, Korea University Guro HospitalDepartment of Internal Medicine, Seoul National University Bundang HospitalDepartment of Thoracic and Cardiovascular Surgery, Cancer Research Institute, Seoul National University College of MedicineDepartment of Oncology, Wuhan Iron and Steel (Group) Corporation Staff-Worker HospitalDepartment of Epidemiology, School of Public Health, China Medical UniversityDepartment of Pulmonary and Critical Care, Chang Gung Memorial HospitalNational Institute of Cancer Research, National Health Research InstitutesDivision of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht UniversityDepartment of Epidemiology and Biostatistics, University of California, San FranciscoMinistry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan UniversitySaw Swee Hock School of Public Health, National University of SingaporeNational Institute of Cancer Research, National Health Research InstitutesDepartment of Pathology, Queen Elizabeth HospitalQujing Center for Diseases Control and PreventionMinistry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan UniversityInstitute of Population Health Sciences, National Health Research InstitutesMinistry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan UniversityDepartment of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical SciencesDivision of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer CenterDivision of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer CenterDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Epidemiology, School of Public Health, Nanjing Medical UniversityDepartment of Epidemiology, School of Public Health, Nanjing Medical UniversityDepartment of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical SciencesDepartment of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical SciencesDepartment of Epidemiology, School of Public Health, China Medical UniversityDepartment of Epidemiology, School of Public Health, China Medical UniversityCenter for Global Health, National Cancer InstituteDivision of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer CenterShanghai Pulmonary HospitalShanghai Pulmonary HospitalShanghai Pulmonary HospitalChina National Environmental Monitoring CenterInstitute of Medicine, Chung Shan Medical UniversityGenomic Research Center, Academia SinicaDepartment of Internal Medicine, National Taiwan University HospitalDepartment of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical SciencesLaboratory Services, American Cancer SocietyDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Medicine, Section of Epidemiology and Population Science, Institute for Clinical and Translational ResearchInstitute of Population Health Sciences, National Health Research InstitutesDepartment of Medicine, Section of Epidemiology and Population Science, Institute for Clinical and Translational ResearchDepartment of Epidemiology, School of Public Health, Nanjing Medical UniversityDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteDivision of Genome Biology, National Cancer Research InstituteDivision of Cancer Epidemiology and Genetics, National Cancer InstituteAbstract 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.https://doi.org/10.1038/s41467-023-38196-z |
| spellingShingle | 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 Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population Nature Communications |
| title | Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population |
| title_full | Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population |
| title_fullStr | Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population |
| title_full_unstemmed | Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population |
| title_short | Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population |
| title_sort | genome wide association study of lung adenocarcinoma in east asia and comparison with a european population |
| url | https://doi.org/10.1038/s41467-023-38196-z |
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