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 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

Pharmaceutical Sciences

Dartmouth College
Université Laval
Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval
National Institutes of Health
University of Pennsylvania
University of Toronto
University of Texas MD Anderson Cancer Center
International Agency for Research on Cancer
Harvard University
Massachusetts General Hospital
University of Copenhagen
University of Hawai'i at Mānoa
University of Göttingen
Vanderbilt University
Case Western Reserve University
University of Oviedo
Centro de Investigación Biomédicaen Red de Epidemiología y Salud Pública (CIBERESP)
Clalit Health Services
Technion-Israel Institute of Technology
Fred Hutchinson Cancer Research Center
University of Sheffield
University of Liverpool
Radboud University Nijmegen
National Institute of Occupational Health
Provincial Health Services Authority
Moffitt Cancer Center
Nanjing Medical University
Seoul National University
University of Pittsburgh
IRCCS Fondazione Ca'Granda – Ospedale Maggiore Policlinico - Milano
University of Milan
University Health Network
University of Southern California
Sejong University
Lund University
Imperial College London
Helenic Health Foundation
Civile-M.P.Arezzo Hospital
Swedish Medical Group
Helmholtz Zentrum München - German Research Center for Environmental Health
Heidelberg University
Translational Lung Research Center Heidelberg (TLRC-H)
University of Salzburg
Umeå University
University of Kentucky
Institute of Pneumology “Marius Nasta”
Charles University
University of Belgrade
Maria Sklodowska-Curie Institute of Oncology
Russian N.N. Blokhin Cancer Research Centre
International Organization for Cancer Prevention and Research
National Institute of Tuberculosis and Lung Diseases
Nofer Institute of Occupational Medicine
University of Bergen
Institute Catala Oncologia
Duke-NUS Medical School
National University of Singapore
Shanghai Cancer Institute
The Institute of Cancer Research
Public Health Ontario
American Cancer Society
Merck
University of British Columbia
University of Groningen
University of Leicester
University Hospitals of Leicester NHS Trust
Baylor College of Medicine

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

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
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-05074-y
State	Published - Dec 1 2018

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10.1038/s41467-018-05074-y

Cite this

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(1), Article 3221. https://doi.org/10.1038/s41467-018-05074-y

@article{f7eb47febf544bdbbb2d175635de6d8e,

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.",

author = "Xuemei Ji and Yohan Boss{\'e} and Landi, \{Maria Teresa\} and Jiang Gui and Xiangjun Xiao and David Qian and Philippe Joubert and Maxime Lamontagne and Yafang Li and Ivan Gorlov and \{de Biasi\}, Mariella and Younghun Han and Olga Gorlova and Hung, \{Rayjean J.\} and Xifeng Wu and James McKay and Xuchen Zong and Robert Carreras-Torres and Christiani, \{David C.\} and Neil Caporaso and Mattias Johansson and Geoffrey Liu and Bojesen, \{Stig E.\} and \{Le Marchand\}, Loic and Demetrios Albanes and Heike Bickeb{\"o}ller and Aldrich, \{Melinda C.\} and Bush, \{William S.\} and Adonina Tardon and Gad Rennert and Chu Chen and Teare, \{M. Dawn\} and Field, \{John K.\} and Kiemeney, \{Lambertus A.\} and Philip Lazarus and Aage Haugen and Stephen Lam and Schabath, \{Matthew B.\} and Andrew, \{Angeline S.\} and Hongbing Shen and Hong, \{Yun Chul\} and Yuan, \{Jian Min\} and Bertazzi, \{Pier A.\} and Pesatori, \{Angela C.\} and Yuanqing Ye and Nancy Diao and Li Su and Ruyang Zhang and Yonathan Brhane and Natasha Leighl and Johansen, \{Jakob S.\} and Anders Mellemgaard and Walid Saliba and Christopher Haiman and Lynne Wilkens and Ana Fernandez-Somoano and Guillermo Fernandez-Tardon and \{van der Heijden\}, \{Erik H.F.M.\} and Kim, \{Jin Hee\} and Juncheng Dai and Zhibin Hu and Davies, \{Michael P.A.\} and Marcus, \{Michael W.\} and Hans Brunnstr{\"o}m and Jonas Manjer and Olle Melander and Muller, \{David C.\} and Kim Overvad and Antonia Trichopoulou and Rosario Tumino and Jennifer Doherty and Goodman, \{Gary E.\} and Angela Cox and Fiona Taylor and Penella Woll and Irene Br{\"u}ske and Judith Manz and Thomas Muley and Angela Risch and Albert Rosenberger and Kjell Grankvist and Mikael Johansson and Frances Shepherd and Tsao, \{Ming Sound\} and Arnold, \{Susanne M.\} and Haura, \{Eric B.\} and Ciprian Bolca and Ivana Holcatova and Vladimir Janout and Milica Kontic and Jolanta Lissowska and Anush Mukeria and Simona Ognjanovic and Orlowski, \{Tadeusz M.\} and Ghislaine Scelo and Beata Swiatkowska and David Zaridze and Per Bakke and Vidar Skaug and Shanbeh Zienolddiny and Duell, \{Eric J.\} and Butler, \{Lesley M.\} and Koh, \{Woon Puay\} and Gao, \{Yu Tang\} and Richard Houlston and John McLaughlin and Victoria Stevens and Nickle, \{David C.\} and Ma{\textquoteright}en Obeidat and Wim Timens and Bin Zhu and Lei Song and Artigas, \{Mar{\'i}a Soler\} and Tobin, \{Martin D.\} and Wain, \{Louise V.\} and Fangyi Gu and Jinyoung Byun and Ahsan Kamal and Dakai Zhu and Tyndale, \{Rachel F.\} and Wei, \{Wei Qi\} and Stephen Chanock and Paul Brennan and Amos, \{Christopher I.\}",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

month = dec,

day = "1",

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

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

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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, 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, MS, 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, WP, Gao, YT, 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, WQ, 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, no. 1, 3221. https://doi.org/10.1038/s41467-018-05074-y

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.

UR - https://www.scopus.com/pages/publications/85051632965

U2 - 10.1038/s41467-018-05074-y

DO - 10.1038/s41467-018-05074-y

M3 - Article

C2 - 30104567

AN - SCOPUS:85051632965

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3221

ER -

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

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