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

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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 & 104 others 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

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 languageEnglish
Article number3221
JournalNature Communications
Volume9
Number of pages15
ISSN2041-1723
DOIs
Publication statusPublished - 2018

    Research areas

  • 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

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