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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 3221 |
| Tidsskrift | Nature Communications |
| Vol/bind | 9 |
| Antal sider | 15 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2018 |
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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; Johansen, Jakob S; Mellemgaard, Anders; Saliba, Walid; Haiman, Christopher; Wilkens, Lynne; Fernandez-Somoano, Ana; Fernandez-Tardon, Guillermo; van der Heijden, Erik H F M; Kim, Jin Hee; Dai, Juncheng; Hu, Zhibin; Davies, Michael P A; Marcus, Michael W; Brunnström, Hans; Manjer, Jonas; Melander, Olle; Muller, David C; Overvad, Kim; Trichopoulou, Antonia; Tumino, Rosario; Doherty, Jennifer; Goodman, Gary E; Cox, Angela; Taylor, Fiona; Woll, Penella; Brüske, Irene; Manz, Judith; Muley, Thomas; Risch, Angela; Rosenberger, Albert; Grankvist, Kjell; Johansson, Mikael; Shepherd, Frances; Tsao, Ming-Sound; Arnold, Susanne M; Haura, Eric B; Bolca, Ciprian; Holcatova, Ivana; Janout, Vladimir; Kontic, Milica; Lissowska, Jolanta; Mukeria, Anush; Ognjanovic, Simona; Orlowski, Tadeusz M; Scelo, Ghislaine; Swiatkowska, Beata; Zaridze, David; Bakke, Per; Skaug, Vidar; Zienolddiny, Shanbeh; Duell, Eric J; Butler, Lesley M; Koh, Woon-Puay; Gao, Yu-Tang; Houlston, Richard; McLaughlin, John; Stevens, Victoria; Nickle, David C; Obeidat, Ma'en; Timens, Wim; Zhu, Bin; Song, Lei; Artigas, María Soler; Tobin, Martin D; Wain, Louise V; Gu, Fangyi; Byun, Jinyoung; Kamal, Ahsan; Zhu, Dakai; Tyndale, Rachel F; Wei, Wei-Qi; Chanock, Stephen; Brennan, Paul; Amos, Christopher I.
I: Nature Communications, Bind 9, 3221, 2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
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
Y1 - 2018
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
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 3221
ER -