Title: | Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes |
Author: | McKay, James D. Hung, Rayjean J. Han, Younghun Zong, Xuchen Carreras Torres, Robert Christiani, David C. Caporaso, Neil E. Johansson, Mattias Xiao, Xiangjun Li, Yafang Byun, Jinyoung Muller, David C. Thorgeirsson, Thorgeir E. Taylor, Fiona Manz, Judith Brhane, Yonathan Leighl, Natasha Shepherd, Frances A. Johansen, Jakob S. Spitz, Margaret R. Rosenberger, Albert Gao, Yu-Tang Haiman, Christopher A. Wilkens, Lynne R. Janout, Vladimir Overvad, Kim Kamal, Ahsan Arnold, Susanne M. Heijden, Henricus F.M. van der Kim, Jin Hee Ognjanovic, Simona Dai, Juncheng Melander, Olle Kontic, Milica Davies, Michael P. A. Marcus, Michael W. Bakke, Per Brunnström, Hans Orlowski, Tadeusz M. Trichopoulou, Antonia Tumino, Rosario Butler, Lesley M. Doherty, Jennifer A. Zhu, Bin Chen, Chu Goodman, Gary E. Lamontagne, Maxime Woll, Penella Bruske, Irene Wichmann, H.-Erich Kachuri, Linda Timens, Wim Grankvist, Kjell Johansson, Mikael B. Wain, Louise V. Rafnar, Thorunn Haura, Eric B. Bolca, Ciprian Bierut, Laura J. Holcátová, Ivana Yuan, Jian-Min Albanes, Demetrius Hancock, Dana B. Lissowska, Jolanta Mukeriya, Anush Bickeböller, Heike Houlston, Richard S. Su, Li Gaddis, Nathan C. Scelo, Ghislaine Swiatkowska, Beata Jiang, Xia Zaridze, David Koh, Woon-Puay Pikielny, Claudio Skaug, Vidar Zienolddiny, Shanbeh Aldrich, Melinda C. Duell, Eric J. Tyndale, Rachel F. McLaughlin, John R. Stevens, Victoria L. Ji, Xuemei Joubert, Philippe Chanock, Stephen J. Nickle, David C. Obeidat, Ma'en Wu, Xifeng Song, Lei Soler Artigas, María Tobin, Martin D. Rennert, Gad Reginsson, Gunnar W. Stefansson, Kari Pooley, Karen A. Kiemeney, Lambertus A. L. M. Lazarus, Philip Lutz, Sharon M. Gu, Fangyi Hong, Yun-Chul Johnson, Eric O. Risch, Angela Haugen, Aage Shen, Hongbing Zhu, Dakai Qian, David C. Diao, Nancy Lindström, Sara Tsao, Ming-Sound Bertazzi, Pier Alberto Chenevix-Trench, Georgia Beesley, Jonathan Mellemgaard, Anders Bossé, Yohan Dunning, Alison M. Zhang, Ruyang Brennan, Paul Landi, Maria Teresa Fernández Somoano, Ana Amos, Christopher I. Saliba, Walid Liu, Geoffrey Timofeeva, Maria N. Hu, Zhibin Bojesen, Stig E. Fernández Tardón, Guillermo Marchand, Loïc Le Bush, William S. Manjer, Jonas Tardón, Adonina Teare, M. Dawn Field, John K. Barnett, Matt Lam, Stephen Schabath, Matthew B. Andrew, Angeline S. SpiroMeta Consortium Cox, Angela Pesatori, Angela Cecilia Ye, Yuanqing Muley, Thomas R. |
Keywords: | Càncer de pulmó Genòmica Lung cancer Genomics |
Issue Date: | 1-Jul-2017 |
Publisher: | Springer Nature |
Abstract: | Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genomewide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1038/ng.3892 |
It is part of: | Nature Genetics, 2017, vol. 49, num. 7, p. 1126-1132 |
URI: | http://hdl.handle.net/2445/124352 |
Related resource: | https://doi.org/10.1038/ng.3892 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
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