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

作者：Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David C. Qian, Philippe Joubert, Maxime Lamontagne, Yafang Li, Ivan P. Gorlov, Mariella De Biasi, Younghun Han, Olga Y. Gorlova, Rayjean J. Hung, Xifeng Wu, James McKay, Xuchen Zong, Robert Carreras‐Torres, David C. Christiani, Neil E. Caporaso, Mattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loı̈c Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardón, 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 Alberto Bertazzi, Angela Cecilia Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha B. Leighl, Jakob Sidenius Johansen, Anders Mellemgaard, Walid Saliba, Christopher A. Haiman, Lynne R. Wilkens, Ana Fernández‐Somoano, Guillermo Fernández‐Tardón, 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 A. Doherty, Gary E. Goodman, Angela Cox, Fiona Taylor, Penella J. Woll, Irene Brüske, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances A. Shepherd, Ming‐Sound Tsao, Susanne M. Arnold, Eric B. Haura, Ciprian Bolca, Ivana Holcátová, Vladimí­r Janout, Milica Kontić, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz Orłowski, Ghislaine Scélo, Beata Świątkowska, Давид Заридзе, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J. Duell, Lesley M. Butler, Woon‐Puay Koh, Yu-Tang Gao, Richard S. Houlston, John McLaughlin, Victoria L. 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 J. Chanock, Paul Brennan, Christopher I. Amos · 发表于：Nature Communications · 年份：2018 · DOI：10.1038/s41467-018-05074-y · 被引用次数：81 · 研究领域：Genetic Associations and Epidemiology、Bioinformatics and Genomic Networks、RNA modifications and cancer

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.