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

Lookup NU author(s): Professor Dawn Teare

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Abstract

© 2018, The Author(s). 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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Author(s): Ji X, Bosse 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, Bickeboller 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, Brunnstrom H, Manjer J, Melander O, Muller DC, Overvad K, Trichopoulou A, Tumino R, Doherty J, Goodman GE, Cox A, Taylor F, Woll P, Bruske 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

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2018

Volume: 9

Issue: 1

Online publication date: 13/08/2018

Acceptance date: 01/05/2018

Date deposited: 12/11/2019

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41467-018-05074-y

DOI: 10.1038/s41467-018-05074-y

PubMed id: 30104567

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