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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
issue
7
pages
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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2018-08-12 04:37:48
@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 Brunnström, Hans and Manjer, Jonas and Melander, Olle and Song, Lei 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},
}