Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.
Qing Lan,Chao A. Hsiung,Keitaro Matsuo,Yun Chul Hong,Adeline Seow,Zhaoming Wang,H. Dean Hosgood,H. Dean Hosgood,Kexin Chen,Jiucun Wang,Nilanjan Chatterjee,Wei Hu,Maria Pik Wong,Wei Zheng,Neil E. Caporaso,Jae Yong Park,Chien-Jen Chen,Yeul Hong Kim,Young Tae Kim,Maria Teresa Landi,Hongbing Shen,Charles E. Lawrence,Laurie Burdett,Meredith Yeager,Jeffrey Yuenger,Kevin B. Jacobs,I. Shou Chang,Tetsuya Mitsudomi,Hee Nam Kim,Gee-Chen Chang,Bryan A. Bassig,Bryan A. Bassig,Margaret A. Tucker,Fusheng Wei,Zhihua Yin,Chen Wu,She-Juan An,Biyun Qian,Victor Ho Fun Lee,Daru Lu,Jianjun Liu,Jianjun Liu,Hyo Sung Jeon,Chin-Fu Hsiao,Jae Sook Sung,Jin Hee Kim,Yu Tang Gao,Ying-Huang Tsai,Yoo Jin Jung,Huan Guo,Zhibin Hu,Amy Hutchinson,Wen Chang Wang,Robert J. Klein,Charles C. Chung,In-Jae Oh,Kuan-Yu Chen,Sonja I. Berndt,Xingzhou He,Wei Wu,Jiang Chang,X. Zhang,Ming Shyan Huang,Hong Zheng,Junwen Wang,Xueying Zhao,Yuqing Li,Jin Eun Choi,Wu Chou Su,Kyong Hwa Park,Sook Whan Sung,Xiao-Ou Shu,Yuh Min Chen,Li Liu,Chang Hyun Kang,Lingmin Hu,Chung Hsing Chen,William Pao,Young-Chul Kim,Tsung-Ying Yang,Jun Xu,Peng Guan,Wen Tan,Jian Su,Chih-Liang Wang,Haixin Li,Alan D. L. Sihoe,Zhenhong Zhao,Ying Chen,Yi Young Choi,Jen Yu Hung,Jun Suk Kim,Ho Il Yoon,Qiuyin Cai,Chien Chung Lin,In Kyu Park,Ping Xu,Jing Dong,Christopher Kim,Qincheng He,Reury Perng Perng,Takashi Kohno,Sun-Seog Kweon,Chih Yi Chen,Roel Vermeulen,Junjie Wu,Wei-Yen Lim,Kun-Chieh Chen,Wong Ho Chow,Bu Tian Ji,John K.C. Chan,Minjie Chu,Yao Jen Li,Jun Yokota,Jihua Li,Hongyan Chen,Yong-Bing Xiang,Chong-Jen Yu,Hideo Kunitoh,Guoping Wu,Li Jin,Yen Li Lo,Kouya Shiraishi,Ying Hsiang Chen,HC Lin,Tangchun Wu,Yi-Long Wu,Pan-Chyr Yang,Baosen Zhou,Min-Ho Shin,Joseph F. Fraumeni,Dongxin Lin,Stephen J. Chanock,Nathaniel Rothman +133 more
TLDR
It is observed that there is no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.Abstract:
To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10(-18)), 6q22.2 (rs9387478, P = 4.14 × 10(-10)) and 6p21.32 (rs2395185, P = 9.51 × 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.read more
Citations
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Iterative Usage of Fixed and Random Effect Models for Powerful and Efficient Genome-Wide Association Studies
Xiaolei Liu,Xiaolei Liu,Meng Huang,Bin Fan,Edward S. Buckler,Edward S. Buckler,Zhiwu Zhang,Zhiwu Zhang +7 more
TL;DR: A new method is named as Fixed and random model Circulating Probability Unification (FarmCPU) that improves statistical power compared to current methods and avoids model over-fitting problem in FEM.
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Global Epidemiology of Lung Cancer
TL;DR: The evidence on lung cancer epidemiology, including data of international scope with comparisons of economically, socially, and biologically different patient groups is reviewed, including a discussion on the epidemiologic characteristics of special groups including women and nonsmokers.
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Risk factors for lung cancer worldwide
TL;DR: Future preventive efforts and research need to focus on non-cigarette tobacco smoking products, as well as better understanding of risk factors underlying lung carcinogenesis in never-smokers.
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Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes
James D. McKay,Rayjean J. Hung,Younghun Han,Xuchen Zong,Robert Carreras-Torres,David C. Christiani,Neil E. Caporaso,Mattias Johansson,Xiangjun Xiao,Yafang Li,Jinyoung Byun,Alison M. Dunning,Karen A. Pooley,David C. Qian,Xuemei Ji,Geoffrey Liu,Maria Timofeeva,Stig E. Bojesen,Stig E. Bojesen,Stig E. Bojesen,Xifeng Wu,Loic Le Marchand,Demetrios Albanes,Heike Bickeböller,Melinda C. Aldrich,William S. Bush,Adonina Tardón,Gad Rennert,M. Dawn Teare,John K. Field,Lambertus A. Kiemeney,Philip Lazarus,Aage Haugen,Stephen Lam,Matthew B. Schabath,Angeline S. Andrew,Hongbing Shen,Yun Chul Hong,Jian-Min Yuan,Pier Alberto Bertazzi,Angela Cecilia Pesatori,Yuanqing Ye,Nancy Diao,Li Su,Ruyang Zhang,Yonathan Brhane,Natasha B. Leighl,Jakob S Johansen,Anders Mellemgaard,Walid Saliba,Christopher A. Haiman,Lynne R. Wilkens,Ana Fernández-Somoano,Guillermo Fernández-Tardón,Henricus F. M. van der Heijden,Jin Hee Kim,Juncheng Dai,Zhibin Hu,Michael P.A. Davies,Michael W. Marcus,Hans Brunnström,Jonas Manjer,Olle Melander,David C. Muller,Kim Overvad,Antonia Trichopoulou,Rosario Tumino,Jennifer A. Doherty,Matt P Barnett,Chu Chen,Gary E. Goodman,Angela Cox,Fiona Taylor,Penella J. Woll,Irene Brüske,H-Erich Wichmann,H-Erich Wichmann,Judith Manz,Thomas Muley,Angela Risch,Albert Rosenberger,Kjell Grankvist,Mikael Johansson,Frances A. Shepherd,Ming-Sound Tsao,Susanne M. Arnold,Eric B. Haura,Ciprian Bolca,Ivana Holcatova,Vladimir Janout,Milica Kontic,Jolanta Lissowska,Anush Mukeria,Simona Ognjanovic,Tadeusz M Orlowski,Ghislaine Scelo,Beata Swiatkowska,David Zaridze,Per Bakke,Vidar Skaug,Shanbeh Zienolddiny,Eric J. Duell,Lesley M. Butler,Woon-Puay Koh,Yu-Tang Gao,Richard S. Houlston,John McLaughlin,Victoria L. Stevens,Philippe Joubert,Maxime Lamontagne,David C. Nickle,Ma'en Obeidat,Wim Timens,Bin Zhu,Lei Song,Linda Kachuri,María Soler Artigas,María Soler Artigas,Martin D. Tobin,Martin D. Tobin,Louise V. Wain,Louise V. Wain,Thorunn Rafnar,Thorgeir E. Thorgeirsson,Gunnar W Reginsson,Kari Stefansson,Dana B. Hancock,Laura J. Bierut,Margaret R. Spitz,Nathan C. Gaddis,Sharon M. Lutz,Fangyi Gu,Eric O. Johnson,Ahsan Kamal,Claudio W. Pikielny,Dakai Zhu,Sara Lindstroem,Xia Jiang,Rachel F. Tyndale,Rachel F. Tyndale,Georgia Chenevix-Trench,Jonathan Beesley,Yohan Bossé,Stephen J. Chanock,Paul Brennan,Maria Teresa Landi,Christopher I. Amos +146 more
TL;DR: 18 susceptibility loci achieving genome-wide significance are identified, including 10 new loci linked with lung cancer overall and six loci associated with lung adenocarcinoma, highlighting the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer.
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Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank
Louise V. Wain,Nick Shrine,Suzanne Miller,Victoria E. Jackson,Ioanna Ntalla,María Soler Artigas,Charlotte K. Billington,Abdul Kader Kheirallah,Richard J. Allen,J. P. Cook,Kelly Probert,Ma'en Obeidat,Yohan Bossé,Ke Hao,Ke Hao,Dirkje S. Postma,Peter D. Paré,Adaikalavan Ramasamy,Adaikalavan Ramasamy,Adaikalavan Ramasamy,Reedik Mägi,Evelin Mihailov,Eva Reinmaa,Erik Melén,Jared O'Connell,Jared O'Connell,Eleni Frangou,Olivier Delaneau,Olivier Delaneau,Colin Freeman,Desislava Petkova,Mark I. McCarthy,Mark I. McCarthy,Ian Sayers,Panos Deloukas,Panos Deloukas,Richard Hubbard,Ian D. Pavord,Anna Hansell,Anna Hansell,Neil C. Thomson,Eleftheria Zeggini,Andrew P. Morris,Jonathan Marchini,Jonathan Marchini,David P. Strachan,Martin D. Tobin,Martin D. Tobin,Ian P. Hall +48 more
TL;DR: By sampling from the extremes of the lung function distribution in UK Biobank, novel genetic causes of lung function and smoking behaviour are identified and substantial shared genetic architecture underlying airflow obstruction is shown across individuals, irrespective of smoking behaviour and other airway disease.
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