Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella de Biasi, Younghun Han, Olga Gorlova, Rayjean J. Hung, Xifeng Wu, James McKay, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil CaporasoMattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, Chu Chen, 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 A. Bertazzi, Angela C. Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl

Research output: Contribution to journalArticle

Abstract

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.

Original languageEnglish
Article number3221
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

chromosomes
Chromosomes
lungs
Lung Neoplasms
Genes
cancer
magnetic permeability
loci
Quantitative Trait Loci
Genome-Wide Association Study
genome
Ligands
genes
Gene Ontology
etiology
annotations
Ontology
ligands
Single Nucleotide Polymorphism
Lung

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk. / Ji, Xuemei; Bossé, Yohan; Landi, Maria Teresa; Gui, Jiang; Xiao, Xiangjun; Qian, David; Joubert, Philippe; Lamontagne, Maxime; Li, Yafang; Gorlov, Ivan; de Biasi, Mariella; Han, Younghun; Gorlova, Olga; Hung, Rayjean J.; Wu, Xifeng; McKay, James; Zong, Xuchen; Carreras-Torres, Robert; Christiani, David C.; Caporaso, Neil; Johansson, Mattias; Liu, Geoffrey; Bojesen, Stig E.; Le Marchand, Loic; Albanes, Demetrios; Bickeböller, Heike; Aldrich, Melinda C.; Bush, William S.; Tardon, Adonina; Rennert, Gad; Chen, Chu; Teare, M. Dawn; Field, John K.; Kiemeney, Lambertus A.; Lazarus, Philip; Haugen, Aage; Lam, Stephen; Schabath, Matthew B.; Andrew, Angeline S.; Shen, Hongbing; Hong, Yun Chul; Yuan, Jian Min; Bertazzi, Pier A.; Pesatori, Angela C.; Ye, Yuanqing; Diao, Nancy; Su, Li; Zhang, Ruyang; Brhane, Yonathan; Leighl, Natasha.

In: Nature Communications, Vol. 9, No. 1, 3221, 01.12.2018.

Research output: Contribution to journalArticle

Ji, X, Bossé, Y, Landi, MT, Gui, J, Xiao, X, Qian, D, Joubert, P, Lamontagne, M, Li, Y, Gorlov, I, de Biasi, M, Han, Y, Gorlova, O, Hung, RJ, Wu, X, McKay, J, Zong, X, Carreras-Torres, R, Christiani, DC, Caporaso, N, Johansson, M, Liu, G, Bojesen, SE, Le Marchand, L, Albanes, D, Bickeböller, H, Aldrich, MC, Bush, WS, Tardon, A, Rennert, G, Chen, C, Teare, MD, Field, JK, Kiemeney, LA, Lazarus, P, Haugen, A, Lam, S, Schabath, MB, Andrew, AS, Shen, H, Hong, YC, Yuan, JM, Bertazzi, PA, Pesatori, AC, Ye, Y, Diao, N, Su, L, Zhang, R, Brhane, Y & Leighl, N 2018, 'Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk', Nature Communications, vol. 9, no. 1, 3221. https://doi.org/10.1038/s41467-018-05074-y
Ji, Xuemei ; Bossé, Yohan ; Landi, Maria Teresa ; Gui, Jiang ; Xiao, Xiangjun ; Qian, David ; Joubert, Philippe ; Lamontagne, Maxime ; Li, Yafang ; Gorlov, Ivan ; de Biasi, Mariella ; Han, Younghun ; Gorlova, Olga ; Hung, Rayjean J. ; Wu, Xifeng ; McKay, James ; Zong, Xuchen ; Carreras-Torres, Robert ; Christiani, David C. ; Caporaso, Neil ; Johansson, Mattias ; Liu, Geoffrey ; Bojesen, Stig E. ; Le Marchand, Loic ; Albanes, Demetrios ; Bickeböller, Heike ; Aldrich, Melinda C. ; Bush, William S. ; Tardon, Adonina ; Rennert, Gad ; Chen, Chu ; Teare, M. Dawn ; Field, John K. ; Kiemeney, Lambertus A. ; Lazarus, Philip ; Haugen, Aage ; Lam, Stephen ; Schabath, Matthew B. ; Andrew, Angeline S. ; Shen, Hongbing ; Hong, Yun Chul ; Yuan, Jian Min ; Bertazzi, Pier A. ; Pesatori, Angela C. ; Ye, Yuanqing ; Diao, Nancy ; Su, Li ; Zhang, Ruyang ; Brhane, Yonathan ; Leighl, Natasha. / Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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abstract = "Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.",
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AU - Bossé, Yohan

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AU - Xiao, Xiangjun

AU - Qian, David

AU - Joubert, Philippe

AU - Lamontagne, Maxime

AU - Li, Yafang

AU - Gorlov, Ivan

AU - de Biasi, Mariella

AU - Han, Younghun

AU - Gorlova, Olga

AU - Hung, Rayjean J.

AU - Wu, Xifeng

AU - McKay, James

AU - Zong, Xuchen

AU - Carreras-Torres, Robert

AU - Christiani, David C.

AU - Caporaso, Neil

AU - Johansson, Mattias

AU - Liu, Geoffrey

AU - Bojesen, Stig E.

AU - Le Marchand, Loic

AU - Albanes, Demetrios

AU - Bickeböller, Heike

AU - Aldrich, Melinda C.

AU - Bush, William S.

AU - Tardon, Adonina

AU - Rennert, Gad

AU - Chen, Chu

AU - Teare, M. Dawn

AU - Field, John K.

AU - Kiemeney, Lambertus A.

AU - Lazarus, Philip

AU - Haugen, Aage

AU - Lam, Stephen

AU - Schabath, Matthew B.

AU - Andrew, Angeline S.

AU - Shen, Hongbing

AU - Hong, Yun Chul

AU - Yuan, Jian Min

AU - Bertazzi, Pier A.

AU - Pesatori, Angela C.

AU - Ye, Yuanqing

AU - Diao, Nancy

AU - Su, Li

AU - Zhang, Ruyang

AU - Brhane, Yonathan

AU - Leighl, Natasha

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