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Record W2887040813 · doi:10.1038/s41467-018-05074-y

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

2018· article· en· W2887040813 on OpenAlexafffund
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, 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, 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, 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

Bibliographic record

VenueNature Communications · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsCentre for Addiction and Mental HealthSt. Paul's HospitalUniversity of British ColumbiaPublic Health OntarioLunenfeld-Tanenbaum Research InstitutePrincess Margaret Cancer CentreBC Cancer AgencyUniversity Health NetworkUniversity of TorontoSinai Health SystemUniversité LavalInstitut universitaire de cardiologie et de pneumologie de Québec
FundersNational Center for Research ResourcesU.S. National Library of MedicineNational Institute of General Medical SciencesNational Cancer InstituteCanadian Institutes of Health ResearchCanadian Cancer Society Research InstituteNational Institutes of HealthNorges ForskningsrådFundación para el Fomento en Asturias de la Investigación Científica Aplicada y la TecnologíaNational Natural Science Foundation of ChinaNational Center for Advancing Translational SciencesNational Human Genome Research InstituteWellcome TrustWorld Health OrganizationRoy Castle Lung Cancer FoundationUniversidad de OviedoPrincess Margaret Hospital FoundationNational Heart, Lung, and Blood InstituteCancer Care Ontario
KeywordsExpression quantitative trait lociGenome-wide association studyKEGGBiologyLung cancerSingle-nucleotide polymorphismQuantitative trait locusGeneticsLocus (genetics)Biological pathwayGenetic associationCandidate geneLung cancer susceptibilityGeneComputational biologyBioinformaticsCancer researchMedicineGene expressionOncologyTranscriptomeGenotype

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.328
Teacher spread0.310 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations81
Published2018
Admission routes2
Has abstractyes

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