University of Leicester
Browse
1/1
5 files

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

journal contribution
posted on 2017-05-12, 15:10 authored by James D. McKay, Rayjean J. Hung, Younghun Han, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil Caporaso, Mattias Johansson, Xiangjun Xiao, Yafang Li, Jinyoung Byun, Xifeng Wu, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, M. Dawn Teare, John K. Field, Jonas Manjer, 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, Olle Melander, Angela C. Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S. Johansen, Anders Mellemgaard, Walid Saliba, David C. Muller, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Henricus F. M. van der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P. A. Davies, Michael W. Marcus, Kim Overvad, Hans Brunnström, Antonia Trichopoulou, Rosario Tumino, Jennifer Doherty, Matt Barnett, Chu Chen, Gary Goodman, Woon-Puay Koh, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, H.-Erich Wichmann, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Yu-Tang Gao, Mikael Johansson, Frances A. Shepherd, Ming-Sound Tsao, Susanne M. Arnold, Eric B. Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Richard Houlston, Anush Mukeria, Simona Ognjanovic, Tadeusz M. Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J. Duell, John McLaughlin, Lesley M. Butler, Victoria Stevens, Philippe Joubert, Maxime Lamontagne, David C. Nickle, Ma’en Obeidat, Wim Timens, Alison Dunning, Bin Zhu, Lei Song, Linda Kachuri, María Soler Artigas, Martin D. Tobin, Louise V. Wain, SpiroMeta Consortium, Thorunn Rafnar, Thorgeir E. Thorgeirsson, Gunnar W. Reginsson, Karen Pooley, 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 Pikielny, David C. Qian, Dakai Zhu, Sara Lindströem, Xia Jiang89, Rachel F. Tyndale, Georgia Chenevix-Trench, Jonathan Beesley, Yohan Bossé, Stephen Chanock, Paul Brennan, Maria Teresa Landi, Xuemei Ji, Christopher I. Amos, Geoffrey Liu, Maria Timofeeva, Stig E. Bojesen
While several lung cancer susceptibility loci have been identified, much of lung cancer heritability 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 GWAS analysis of lung cancer on 29,266 patients and 56,450 controls. We identified 18 susceptibility loci achieving genome wide significance, including 10 novel loci. The novel loci highlighted the striking heterogeneity in genetic susceptibility across lung cancer histological subtypes, with four loci associated with lung cancer overall and six with lung adenocarcinoma. Gene expression quantitative trait analysis (eQTL) in 1,425 normal lung tissues highlighted 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.

History

Citation

Nature Genetics, 2017, 49, pp. 1126–1132

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Health Sciences

Version

  • AM (Accepted Manuscript)

Published in

Nature Genetics

Publisher

Nature Publishing Group

issn

1061-4036

eissn

1546-1718

Acceptance date

2017-05-10

Copyright date

2017

Available date

2017-12-12

Publisher version

https://www.nature.com/ng/journal/v49/n7/full/ng.3892.html

Notes

The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en

Usage metrics

    University of Leicester Publications

    Categories

    No categories selected

    Keywords

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC