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Record W2905137810 · doi:10.1016/s2213-2600(18)30389-8

Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

2018· article· en· W2905137810 on OpenAlexaff
Nick Shrine, Michael A. Portelli, Catherine John, María Soler Artigas, Neil Bennett, Robert J. Hall, Jon Lewis, Amanda P. Henry, Charlotte K. Billington, Azaz Ahmad, Richard Packer, Dominick Shaw, Zara Pogson, Andrew Fogarty, Tricia M. McKeever, Amisha Singapuri, Liam G. Heaney, Adel Mansur, Rekha Chaudhuri, Neil C. Thomson, John W. Holloway, Gabrielle A. Lockett, Peter Howarth, Ratko Djukanović, Jenny Hankinson, Robert Niven, Angela Simpson, Kian Fan Chung, Peter J. Sterk, John Blakey, Ian M. Adcock, Sile Hu, Yike Guo, Ma’en Obeidat, Don D. Sin, Maarten van den Berge, David C. Nickle, Yohan Bossé, Martin D. Tobin, Ian P. Hall, Christopher E. Brightling, Louise V. Wain, Ian Sayers

Bibliographic record

VenueThe Lancet Respiratory Medicine · 2018
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsInstitut universitaire de cardiologie et de pneumologie de QuébecUniversité LavalSt. Paul's HospitalUniversity of British Columbia
FundersMedical Research CouncilGlaxoSmithKlineAsthma and Lung UKVirginia Commonwealth UniversityTeva Pharmaceutical IndustriesNational Institute for Health and Care ResearchDepartment of Chemical Engineering and Biotechnology, University of CambridgeRegeneron PharmaceuticalsPfizerBritish Lung FoundationRosetrees TrustSanofiAstraZenecaAmgen
KeywordsAsthmaMedicineBiobankGenome-wide association studyCohortGenetic associationStage (stratigraphy)Internal medicineSingle-nucleotide polymorphismBioinformaticsGeneticsGenotypeGeneBiology

Abstract

fetched live from OpenAlex

BACKGROUND: Few genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel genetic variants associated with moderate-to-severe asthma, see whether previously identified genetic variants for all types of asthma contribute to moderate-to-severe asthma, and provide novel mechanistic insights using expression analyses in patients with asthma. METHODS: . For novel signals, we investigated their effect on all types of asthma (mild, moderate, and severe). For all signals meeting genome-wide significance, we investigated their effect on gene expression in patients with asthma and controls. FINDINGS: ) and MUC5AC mRNA was increased in bronchial epithelial samples from patients with severe asthma (in two independent analyses, p=0·039 and p=0·022). INTERPRETATION: We found substantial shared genetic architecture between mild and moderate-to-severe asthma. We also report for the first time genetic variants associated with the risk of developing moderate-to-severe asthma that regulate mucin production. Finally, we identify candidate causal genes in these loci and provide increased insight into this difficult to treat population. FUNDING: Asthma UK, AirPROM, U-BIOPRED, UK Medical Research Council, and Rosetrees Trust.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation 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 score0.063
Threshold uncertainty score0.617

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.057
GPT teacher head0.329
Teacher spread0.271 · 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 teacher head, 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

Citations257
Published2018
Admission routes1
Has abstractyes

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