ArticleHuman molecular genetics2015
Integrative pathway genomics of lung function and airflow obstruction.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.Nature communications · 2018Pooled it
- Gene set enrichment analysis to create polygenic scores: a developmental examination of aggression.Translational psychiatry · 2019Trial
- Serum proteomics links the cardiorespiratory biomarkers CTRC, OSM, and MMP-10 to exacerbation severity and number in patients with COPD.Clinical science (London, England : 1979) · 2025Article
- Multi-omic association study identifies DNA methylation-mediated genotype and smoking exposure effects on lung function in children living in urban settings.PLoS genetics · 2023Article
- Getting to the How and Why: Are Individuals with Chronic Obstructive Pulmonary Disease More Susceptible to the Health Effects of Air Pollution Exposure?American journal of respiratory and critical care medicine · 2022Article
- Air, Land, and Sea: Gene-Environment Interaction in Chronic Disease.The American journal of medicine · 2021Review
- Recent advances in chronic obstructive pulmonary disease pathogenesis: from disease mechanisms to precision medicine.The Journal of pathology · 2020Review
- Potential Crosstalk between Liver and Extra-liver Organs in Mouse Models of Acute Liver Injury.International journal of biological sciences · 2020Article
- Pneumonia: host susceptibility and shared genetics with pulmonary function and other traits.Clinical and experimental immunology · 2019Article
- Differential coexpression networks in bronchiolitis and emphysema phenotypes reveal heterogeneous mechanisms of chronic obstructive pulmonary disease.Journal of cellular and molecular medicine · 2019Article
- Molecular predictors of brain metastasis-related microRNAs in lung adenocarcinoma.PLoS genetics · 2019Article
- Effect of SNPs in HSP Family Genes, Variation in the mRNA and Intracellular Hsp Levels in COPD Secondary to Tobacco Smoking and Biomass-Burning Smoke.Frontiers in genetics · 2019Article
- Matrix metalloproteinases in emphysema.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Article
- Matrix Metalloproteinase-28 Is a Key Contributor to Emphysema Pathogenesis.The American journal of pathology · 2017Article
- Article
- Interplay of extracellular matrix and leukocytes in lung inflammation.Cellular immunology · 2017Review
- Lung function discordance in monozygotic twins and associated differences in blood DNA methylation.Clinical epigenetics · 2017Article
- Article
- Stromelysin-2 (MMP10) Moderates Inflammation by Controlling Macrophage Activation.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
51 authors at 20 institutions in 13 countries.
Funding
Abstract
Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating pathway-based methods with GWASs of pulmonary function and airflow obstruction would identify a broader repertoire of genes and processes influencing these traits. We performed two independent GWASs of lung function and applied gene set enrichment analysis to one of the studies and validated the results using the second GWAS. We identified 131 significantly enriched gene sets associated with lung function and clustered them into larger biological modules involved in diverse processes including development, immunity, cell signaling, proliferation and arachidonic acid. We found that enrichment of gene sets was not driven by GWAS-significant variants or loci, but instead by those with less stringent association P-values. Next, we applied pathway enrichment analysis to a meta-analyzed GWAS of airflow obstruction. We identified several biologic modules that functionally overlapped with those associated with pulmonary function. However, differences were also noted, including enrichment of extracellular matrix (ECM) processes specifically in the airflow obstruction study. Network analysis of the ECM module implicated a candidate gene, matrix metalloproteinase 10 (MMP10), as a putative disease target. We used a knockout mouse model to functionally validate MMP10's role in influencing lung's susceptibility to cigarette smoke-induced emphysema. By integrating pathway analysis with population-based genomics, we unraveled biologic processes underlying pulmonary function traits and identified a candidate gene for obstructive lung disease.
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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.