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Record W2977245743 · doi:10.1002/ijc.32698

Genome‐wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk

2019· review· en· W2977245743 on OpenAlexaff
Juncheng Dai, Mingtao Huang, Christopher I. Amos, Adonina Tardón, Angeline S. Andrew, Chu Chen, David C. Christiani, Demetrius Albanes, Gad Rennert, Jingyi Fan, Gary E. Goodman, Geoffrey Liu, John K. Field, Kjell Grankvist, Lambertus A. Kiemeney, Loı̈c Le Marchand, Matthew B. Schabath, Mattias Johansson, Melinda C. Aldrich, Mikael Johansson, Neil E. Caporaso, Philip Lazarus, Stephan Lam, Stig E. Bojesen, Susanne M. Arnold, Maria Teresa Landi, Angela Risch, H‐Erich Wichmann, Heike Bickeböller, Paul Brennan, Sanjay Shete, Olle Melander, Hans Brunnström, Shan Zienolddiny, Penella J. Woll, Victoria L. Stevens, Zhibin Hu, Hongbing Shen

Bibliographic record

VenueInternational Journal of Cancer · 2019
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsBC Cancer AgencyPrincess Margaret Cancer CentreSinai Health SystemLunenfeld-Tanenbaum Research Institute
FundersNational Cancer InstituteNational Institutes of HealthWorld Health Organization
KeywordsIndelLung cancerGeneticsGenome-wide association studyBiologyCancerMedicineOncologyGeneSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

Genome‐wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large‐scale samples have been available to systematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large‐scale meta‐analysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional annotations were performed to further explore the potential function of lung cancer risk INDELs. Conditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci were identified in genome‐wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 × 10−8; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 × 10−7; 12p13.31: rs71450133, Deletion, OR = 1.09, p = 8.83 × 10−7; and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 × 10−8). The eQTL analysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by regulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, the INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be potentially functional genetic variants for lung cancer risk. Further functional experiments are needed to better understand INDEL mechanisms in carcinogenesis.

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)0.002
metaresearch head score (Gemma)0.003
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: Review · Consensus signal: none
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.003
Bibliometrics0.0020.003
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.039
GPT teacher head0.373
Teacher spread0.334 · 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
GenreReview

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

Citations22
Published2019
Admission routes1
Has abstractyes

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