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

McKay, James D.; Hung, Rayjean J.; Han, Younghun; Zong, Xuchen; Carreras-Torres, Robert; Christiani, David C.; Caporaso, Neil E; Johansson, Mattias; Xiao, Xiangjun and Li, Yafang, et al. (2017) In Nature Genetics 49(7). p.1126-1132
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 genome-wide 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)... (More)

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 genome-wide 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.

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Nature Genetics
volume
49
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7
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7 pages
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Nature Publishing Group
external identifiers
  • wos:000404253300024
  • scopus:85020451435
ISSN
1546-1718
DOI
10.1038/ng.3892
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English
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yes
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b5f6bb50-9652-4fb7-821f-5e126bc11baa
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2017-07-13 09:45:30
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2017-09-20 09:47:51
@article{b5f6bb50-9652-4fb7-821f-5e126bc11baa,
  abstract     = {<p>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 genome-wide 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.</p>},
  author       = {McKay, James D. and Hung, Rayjean J. and Han, Younghun and Zong, Xuchen and Carreras-Torres, Robert and Christiani, David C. and Caporaso, Neil E and Johansson, Mattias and Xiao, Xiangjun and Li, Yafang and Byun, Jinyoung and Dunning, Alison and Pooley, Karen A and Qian, David C and Ji, Xuemei and Liu, Geoffrey and Timofeeva, Maria N and Bojesen, Stig E. and Wu, Xifeng and Le Marchand, Loic and Albanes, Demetrios and Bickeböller, Heike and Aldrich, Melinda C and Bush, William S and Tardon, Adonina and Rennert, Gad and Teare, M Dawn and Field, John K. and Kiemeney, Lambertus A. and Lazarus, Philip and Haugen, Aage and Lam, Stephen and Schabath, Matthew B and Andrew, Angeline S and Shen, Hongbing and Hong, Yun-Chul and Yuan, Jian-Min and Bertazzi, Pier Alberto and Pesatori, Angela C and Ye, Yuanqing and Diao, Nancy and Su, Li and Zhang, Ruyang and Brhane, Yonathan and Leighl, Natasha and Johansen, Jakob S and Mellemgaard, Anders and Saliba, Walid and Haiman, Christopher A and Wilkens, Lynne R. and Fernandez-Somoano, Ana and Fernandez-Tardon, Guillermo and van der Heijden, Henricus F M and Kim, Jin Hee and Dai, Juncheng and Hu, Zhibin and Davies, Michael P A and Marcus, Michael W and Brunnström, Hans and Manjer, Jonas and Melander, Olle and Muller, David C and Overvad, Kim and Trichopoulou, Antonia and Tumino, Rosario and Doherty, Jennifer A and Barnett, Matt P and Chen, Chu and Goodman, Gary E and Cox, Angela and Taylor, Fiona and Woll, Penella and Brüske, Irene and Wichmann, H-Erich and Manz, Judith and Muley, Thomas R and Risch, Angela and Rosenberger, Albert and Grankvist, Kjell and Johansson, Mikael and Shepherd, Frances A and Tsao, Ming-Sound and Arnold, Susanne M and Haura, Eric B and Bolca, Ciprian and Holcatova, Ivana and Janout, Vladimir and Kontic, Milica and Lissowska, Jolanta and Mukeria, Anush and Ognjanovic, Simona and Orlowski, Tadeusz M and Scelo, Ghislaine and Swiatkowska, Beata and Zaridze, David and Bakke, Per and Skaug, Vidar and Zienolddiny, Shanbeh and Duell, Eric J. and Butler, Lesley M and Koh, Woon-Puay and Gao, Yu-Tang and Houlston, Richard S. and McLaughlin, John R and Stevens, Victoria L. and Joubert, Philippe and Lamontagne, Maxime and Nickle, David C and Obeidat, Ma'en and Timens, Wim and Zhu, Bin and Song, Lei and Kachuri, Linda and Artigas, María Soler and Tobin, Martin D and Wain, Louise V. and Rafnar, Thorunn and Thorgeirsson, Thorgeir E and Reginsson, Gunnar W and Stefansson, Kari and Hancock, Dana B and Bierut, Laura J and Spitz, Margaret R and Gaddis, Nathan C and Lutz, Sharon M and Gu, Fangyi and Johnson, Eric O and Kamal, Ahsan and Pikielny, Claudio and Zhu, Dakai and Lindströem, Sara and Jiang, Xia and Tyndale, Rachel F and Chenevix-Trench, Georgia and Beesley, Jonathan and Bossé, Yohan and Chanock, Stephen and Brennan, Paul and Landi, Maria Teresa and Amos, Christopher I and , },
  issn         = {1546-1718},
  language     = {eng},
  number       = {7},
  pages        = {1126--1132},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes},
  url          = {http://dx.doi.org/10.1038/ng.3892},
  volume       = {49},
  year         = {2017},
}