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

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...

Full description

Saved in:

Bibliographic Details
Published in:	Nature communications Vol. 9; no. 1; pp. 3221 - 15
Main Authors:	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, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Davies, Michael P. A., Marcus, Michael W., Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brüske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Koh, Woon-Puay, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma’en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, María Soler, Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Chanock, Stephen, Amos, Christopher I.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 13.08.2018 Nature Publishing Group Nature Portfolio
Subjects:	38/39 38/43 45/43 631/208/199 631/208/2490 631/208/68 631/67/1612 631/67/68 Adolescent Adult Aged Annotations Basic Medicine Cancer Cancer and Oncology Cancer och onkologi Channel gating Child Child, Preschool Chromosome 15 Chromosomes Chromosomes, Human, Pair 15 - genetics Clinical Medicine Cohort Studies Etiology Female Gene mapping Gene Ontology Gene Regulatory Networks Genetic Predisposition to Disease Genome-wide association studies Genomes Health risk assessment Health risks Humanities and Social Sciences Humans Infant Infant, Newborn Klinisk medicin Ligands Lung cancer Lung Neoplasms - genetics Male Medical and Health Sciences Medical Genetics and Genomics (including Gene Therapy) Medicin och hälsovetenskap Medicinsk genetik och genomik (Här ingår: Genterapi) Medicinska och farmaceutiska grundvetenskaper Middle Aged multidisciplinary Polymorphism, Single Nucleotide Quantitative trait loci Quantitative Trait Loci - genetics Reproducibility of Results Risk Risk Factors Science Science (multidisciplinary) Single-nucleotide polymorphism Smoking - adverse effects Young Adult
ISSN:	2041-1723, 2041-1723
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. The chromosome 15q25.1 locus is a leading susceptibility region for lung cancer. Here, the authors interrogate three GWAS cohorts with 42,901 individuals to investigate potential pathological pathways such as gated channel activity and neuroactive ligand receptor interaction in lung cancer etiology.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-018-05074-y