Genome-Wide Association Studies Identify <i>CHRNA5/3</i> and <i>HTR4</i> in the Development of Airflow Obstruction
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
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.
- Candidate categories
- none
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: Other designConsensus signal: none
- Genre
- Candidate signal: ReviewConsensus signal: Review
- Teacher disagreement score
- 0.958
- Threshold uncertainty score
- 0.476
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.326 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
RATIONALE: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. OBJECTIVES: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. METHODS: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV(1) and its ratio to FVC (FEV(1)/FVC) both less than their respective lower limits of normal as determined by published reference equations. MEASUREMENTS AND MAIN RESULTS: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV(1)/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis. CONCLUSIONS: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction.
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.
The record
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Topic
- Genetic Associations and Epidemiology
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Lunenfeld-Tanenbaum Research InstituteOntario Institute for Cancer Research
- Funders
- National Center for Research ResourcesNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteNIHR Cambridge Biomedical Research CentreNational Institute of Diabetes and Digestive and Kidney DiseasesCambridge Institute for Medical Research, University of CambridgeEngineering and Physical Sciences Research CouncilNational Center for Advancing Translational SciencesMedical Research CouncilAbbott DiagnosticsCenters for Medicare and Medicaid ServicesAgency for Healthcare Research and QualityNational Institute on AgingNational Institute for Health and Care ResearchCentre for Cognitive Ageing and Cognitive EpidemiologyEconomic and Social Research CouncilCOPD FoundationBundesamt für GesundheitBiotechnology and Biological Sciences Research CouncilCancer Research UKWellcome TrustAXA Research FundNational Institutes of HealthU.S. Department of Veterans AffairsSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Institute of Environmental Health SciencesHjartaverndLungenliga SchweizEuropean CommissionAge UKNederlandse Organisatie voor Wetenschappelijk OnderzoekFreiwillige Akademische GesellschaftJohns Hopkins UniversityNational Health and Medical Research CouncilAstraZenecaDirectorate for Biological SciencesGlaxoSmithKlineChinese Society of Clinical OncologyJuvenile Diabetes Research Foundation InternationalUniversity of EdinburghNational Science Foundation
- Keywords
- Genome-wide association studyMedicineSingle-nucleotide polymorphismCOPDMeta-analysisPopulationSpirometryAsthmaGenetic associationGeneticsAirway obstructionInternal medicineGeneGenotypeBiologyAirwaySurgeryEnvironmental health
- Has abstract in OpenAlex
- yes