SynthesisAmerican journal of respiratory and critical care medicine2012
Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction.
Synthesis in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
112 citing papers in PubMed, 5 syntheses or guidelines pooled it, 175 citations in OpenAlex.
- Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.PLoS genetics · 2019Pooled it
- IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.American journal of respiratory cell and molecular biology · 2015Pooled it
- APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema.The European respiratory journal · 2014Pooled it
- Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis.The Lancet. Respiratory medicine · 2014Pooled it
- Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.PloS one · 2014Pooled it
- A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.BMC genetics · 2015Trial
- Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide.Annals of the American Thoracic Society · 2014Trial
- Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility.Human genetics · 2013Trial
- Genome-wide association study of image-based emphysema scoring in the Swedish CArdioPulmonary bioImage Study (SCAPIS) suggests two new risk loci in smokers.Respiratory research · 2026Article
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- Exploring the Intervention Mechanism of Effective-Component Combination of Bufei Yishen Formula III for Airway Epithelial Barrier Injury: A miRNA-mRNA Regulatory Network Analysis.Journal of inflammation research · 2025Article
- Genome-wide analysis in northern Chinese twins identifies twelve new susceptibility loci for pulmonary function.BMC genomics · 2024Article
- A novel phenotype imputation method with copula model.BMC bioinformatics · 2024Article
- Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in a Mouse Knockout Model.Lung · 2024Article
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- Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in Mouse.Research square · 2024Article
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- Animal models: An essential tool to dissect the heterogeneity of chronic obstructive pulmonary disease.Journal of translational internal medicine · 2023Article
- Biological and Genetic Mechanisms of COPD, Its Diagnosis, Treatment, and Relationship with Lung Cancer.Biomedicines · 2023Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
79 authors at 20 institutions in 10 countries.
Funding
Abstract
rationaleGenome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.
objectivesPerform 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.
methodsFifteen 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
resultsThe 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.
conclusionsThese 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.