Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk.
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Publication Date
2018-08-13ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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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Licenseref URL
http://creativecommons.org/licenses/by/4.0/Version of record
Subject
Chromosomes, Human, Pair 15
Humans
Lung Neoplasms
Genetic Predisposition to Disease
Risk Factors
Cohort Studies
Reproducibility of Results
Smoking
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Adolescent
Adult
Aged
Middle Aged
Child
Child, Preschool
Infant
Infant, Newborn
Female
Male
Gene Regulatory Networks
Young Adult
Gene Ontology
Research team
Cancer Genomics
Language
eng
Date accepted
2018-05-01
License start date
2018-08-13
Citation
Nature communications, 2018, 9 (1), pp. 3221 - ?