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Record W4210547181 · doi:10.1093/hmg/ddac030

Genome-wide interaction analysis identified low-frequency variants with sex disparity in lung cancer risk

2022· article· en· W4210547181 on OpenAlexaff
Yafang Li, Xiangjun Xiao, Jianrong Li, Jinyoung Byun, Chao Cheng, Yohan Bossé, James McKay, Demetrius Albanes, Stephen Lam, Adonina Tardón, Chu Chen, Stig E. Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H‐Erich Wichmann, David C. Christiani, Gad Rennert, Susanne M. Arnold, Gary E. Goodman, John K. Field, Michael P.A. Davies, Sanjay Shete, Loı̈c Le Marchand, Olle Melander, Hans Brunnström, Geoffrey Liu, Angeline S. Andrew, Lambertus A. Kiemeney, Hongbing Shen, Ryan Sun, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E. Caporaso, M. Dawn Teare, Yun‐Chul Hong, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Ann G. Schwartz, Ivan P. Gorlov, Kristen S. Purrington, Ping Yang, Yanhong Liu, Younghun Han, Joan E. Bailey‐Wilson, Susan M. Pinney, Diptasri Mandal, James C. Willey, Colette Gaba, Paul Brennan, Christopher I. Amos

Bibliographic record

VenueHuman Molecular Genetics · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsSinai Health SystemLunenfeld-Tanenbaum Research InstituteUniversity of TorontoUniversity Health NetworkPublic Health OntarioUniversity of British ColumbiaPrincess Margaret Cancer CentreUniversité LavalInstitut universitaire de cardiologie et de pneumologie de Québec
FundersCommon FundNational Institute of Environmental Health SciencesNational Institute on Drug AbuseDivision of Cancer Epidemiology and Genetics, National Cancer InstituteNational Institute of Neurological Disorders and StrokeNational Heart, Lung, and Blood InstituteNational Institute of Mental HealthNIH Office of the DirectorNational Cancer InstituteU.S. Department of Health and Human ServicesNational Institutes of HealthCancer Prevention and Research Institute of TexasNational Human Genome Research InstituteWorld Health Organization
KeywordsLung cancerBiologyGenome-wide association studyOdds ratioGenetic associationGenotypeCancerSexual dimorphismGeneticsAllele frequencyOncologyInternal medicineSingle-nucleotide polymorphismGeneEndocrinologyMedicine

Abstract

fetched live from OpenAlex

Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene-sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry. Three low-frequency variants (minor allele frequency < 0.05), rs17662871 [odds ratio (OR) = 0.71, P = 4.29×10-8); rs79942605 (OR = 2.17, P = 2.81×10-8) and rs208908 (OR = 0.70, P = 4.54×10-8) were identified with different risk effect of lung cancer between men and women. Further expression quantitative trait loci and functional annotation analysis suggested rs208908 affects lung cancer risk through differential regulation of Coxsackie virus and adenovirus receptor gene expression in lung tissues between men and women. Our study is one of the first studies to provide novel insights about the genetic and molecular basis for sex disparity in lung cancer development.

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)0.001
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 score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.000

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 head0.009
GPT teacher head0.278
Teacher spread0.270 · 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

Citations7
Published2022
Admission routes1
Has abstractyes

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