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 Caporaso; Mattias 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; Jakob S Johansen; Anders Mellemgaard; Walid Saliba; Christopher Haiman; Lynne Wilkens; Ana Fernandez-Somoano; Guillermo Fernandez-Tardon; Erik H F M van der Heijden; Jin Hee Kim; Juncheng Dai; Zhibin Hu; Michael P A Davies; Michael W Marcus; Hans Brunnström; Jonas Manjer; Olle Melander; David C Muller; Kim Overvad; Antonia Trichopoulou; Rosario Tumino; Jennifer Doherty; Gary E Goodman; Angela Cox; Fiona Taylor; Penella Woll; Irene Brüske; Judith Manz; Thomas Muley; Angela Risch; Albert Rosenberger; Kjell Grankvist; Mikael Johansson; Frances Shepherd; Ming-Sound Tsao; Susanne M Arnold; Eric B Haura; Ciprian Bolca; Ivana Holcatova; Vladimir Janout; Milica Kontic; Jolanta Lissowska; Anush Mukeria; Simona Ognjanovic; Tadeusz M Orlowski; Ghislaine Scelo; Beata Swiatkowska; David Zaridze; Per Bakke; Vidar Skaug; Shanbeh Zienolddiny; Eric J Duell; Lesley M Butler; Woon-Puay Koh; Yu-Tang Gao; Richard Houlston; John McLaughlin; Victoria Stevens; David C Nickle; Ma'en Obeidat; Wim Timens; Bin Zhu; Lei Song; María Soler Artigas; Martin D Tobin; Louise V Wain; Fangyi Gu; Jinyoung Byun; Ahsan Kamal; Dakai Zhu; Rachel F Tyndale; Wei-Qi Wei; Stephen Chanock; Paul Brennan; Christopher I Amos

doi:10.1038/s41467-018-05074-y

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, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M van der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer Doherty, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Woon-Puay Koh, Yu-Tang Gao, Richard Houlston, John McLaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, María Soler Artigas, Martin D Tobin, Louise V Wain, Fangyi Gu, Jinyoung Byun, Ahsan Kamal, Dakai Zhu, Rachel F Tyndale, Wei-Qi Wei, Stephen Chanock, Paul Brennan, Christopher I Amos

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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.

Original language	English
Article number	3221
Journal	Nature Communications
Volume	9
Number of pages	15
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-018-05074-y
Publication status	Published - 1 Dec 2018

Keywords

Adolescent
Adult
Aged
Child
Child, Preschool
Chromosomes, Human, Pair 15/genetics
Cohort Studies
Female
Gene Ontology
Gene Regulatory Networks
Genetic Predisposition to Disease
Humans
Infant
Infant, Newborn
Lung Neoplasms/genetics
Male
Middle Aged
Polymorphism, Single Nucleotide
Quantitative Trait Loci/genetics
Reproducibility of Results
Risk Factors
Smoking/adverse effects
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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s41467-018-05074-yFinal published version, 1.38 MBLicence: CC BY

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Ji, X., Bossé, Y., Landi, M. T., Gui, J., Xiao, X., Qian, D., Joubert, P., Lamontagne, M., Li, Y., Gorlov, I., de Biasi, M., Han, Y., Gorlova, O., Hung, R. J., Wu, X., McKay, J., Zong, X., Carreras-Torres, R., Christiani, D. C., ... Amos, C. I. (2018). Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk. Nature Communications, 9, Article 3221. https://doi.org/10.1038/s41467-018-05074-y

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, Y-C, Yuan, J-M, Bertazzi, PA, Pesatori, AC, Ye, Y, Diao, N, Su, L, Zhang, R, Brhane, Y, Leighl, N, Johansen, JS, Mellemgaard, A, Saliba, W, Haiman, C, Wilkens, L, Fernandez-Somoano, A, Fernandez-Tardon, G, van der Heijden, EHFM, Kim, JH, Dai, J, Hu, Z, Davies, MPA, Marcus, MW, Brunnström, H, Manjer, J, Melander, O, Muller, DC, Overvad, K, Trichopoulou, A, Tumino, R, Doherty, J, Goodman, GE, Cox, A, Taylor, F, Woll, P, Brüske, I, Manz, J, Muley, T, Risch, A, Rosenberger, A, Grankvist, K, Johansson, M, Shepherd, F, Tsao, M-S, Arnold, SM, Haura, EB, Bolca, C, Holcatova, I, Janout, V, Kontic, M, Lissowska, J, Mukeria, A, Ognjanovic, S, Orlowski, TM, Scelo, G, Swiatkowska, B, Zaridze, D, Bakke, P, Skaug, V, Zienolddiny, S, Duell, EJ, Butler, LM, Koh, W-P, Gao, Y-T, Houlston, R, McLaughlin, J, Stevens, V, Nickle, DC, Obeidat, M, Timens, W, Zhu, B, Song, L, Artigas, MS, Tobin, MD, Wain, LV, Gu, F, Byun, J, Kamal, A, Zhu, D, Tyndale, RF, Wei, W-Q, Chanock, S, Brennan, P & Amos, CI 2018, 'Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk', Nature Communications, vol. 9, 3221. https://doi.org/10.1038/s41467-018-05074-y

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

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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year = "2018",

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doi = "10.1038/s41467-018-05074-y",

language = "English",

volume = "9",

journal = "Nature Communications",

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TY - JOUR

T1 - Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

AU - Ji, Xuemei

AU - Bossé, Yohan

AU - Landi, Maria Teresa

AU - Gui, Jiang

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

AU - Johansen, Jakob S

AU - Mellemgaard, Anders

AU - Saliba, Walid

AU - Haiman, Christopher

AU - Wilkens, Lynne

AU - Fernandez-Somoano, Ana

AU - Fernandez-Tardon, Guillermo

AU - van der Heijden, Erik H F M

AU - Kim, Jin Hee

AU - Dai, Juncheng

AU - Hu, Zhibin

AU - Davies, Michael P A

AU - Marcus, Michael W

AU - Brunnström, Hans

AU - Manjer, Jonas

AU - Melander, Olle

AU - Muller, David C

AU - Overvad, Kim

AU - Trichopoulou, Antonia

AU - Tumino, Rosario

AU - Doherty, Jennifer

AU - Goodman, Gary E

AU - Cox, Angela

AU - Taylor, Fiona

AU - Woll, Penella

AU - Brüske, Irene

AU - Manz, Judith

AU - Muley, Thomas

AU - Risch, Angela

AU - Rosenberger, Albert

AU - Grankvist, Kjell

AU - Johansson, Mikael

AU - Shepherd, Frances

AU - Tsao, Ming-Sound

AU - Arnold, Susanne M

AU - Haura, Eric B

AU - Bolca, Ciprian

AU - Holcatova, Ivana

AU - Janout, Vladimir

AU - Kontic, Milica

AU - Lissowska, Jolanta

AU - Mukeria, Anush

AU - Ognjanovic, Simona

AU - Orlowski, Tadeusz M

AU - Scelo, Ghislaine

AU - Swiatkowska, Beata

AU - Zaridze, David

AU - Bakke, Per

AU - Skaug, Vidar

AU - Zienolddiny, Shanbeh

AU - Duell, Eric J

AU - Butler, Lesley M

AU - Koh, Woon-Puay

AU - Gao, Yu-Tang

AU - Houlston, Richard

AU - McLaughlin, John

AU - Stevens, Victoria

AU - Nickle, David C

AU - Obeidat, Ma'en

AU - Timens, Wim

AU - Zhu, Bin

AU - Song, Lei

AU - Artigas, María Soler

AU - Tobin, Martin D

AU - Wain, Louise V

AU - Gu, Fangyi

AU - Byun, Jinyoung

AU - Kamal, Ahsan

AU - Zhu, Dakai

AU - Tyndale, Rachel F

AU - Wei, Wei-Qi

AU - Chanock, Stephen

AU - Brennan, Paul

AU - Amos, Christopher I

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Child

KW - Child, Preschool

KW - Chromosomes, Human, Pair 15/genetics

KW - Cohort Studies

KW - Female

KW - Gene Ontology

KW - Gene Regulatory Networks

KW - Genetic Predisposition to Disease

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Lung Neoplasms/genetics

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci/genetics

KW - Reproducibility of Results

KW - Risk Factors

KW - Smoking/adverse effects

KW - Young Adult

U2 - 10.1038/s41467-018-05074-y

DO - 10.1038/s41467-018-05074-y

M3 - Journal article

C2 - 30104567

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 3221

ER -

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

Abstract

Keywords

UN SDGs

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