ArticleAmerican journal of respiratory and critical care medicine2016
Exome Sequencing Analysis in Severe, Early-Onset Chronic Obstructive Pulmonary Disease.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Proper conditional analysis in the presence of missing data: Application to large scale meta-analysis of tobacco use phenotypes.PLoS genetics · 2018Pooled it
- Genetic variants in pulmonary hypertension associated with chronic obstructive pulmonary disease.Current opinion in pulmonary medicine · 2026Review
- Evaluation of Pulmonary Fibrosis Outcomes by Race and Ethnicity in US Adults.JAMA network open · 2023Article
- Definition and Nomenclature of Chronic Obstructive Pulmonary Disease: Time for Its Revision.American journal of respiratory and critical care medicine · 2022Article
- Assessing the contribution of rare genetic variants to phenotypes of chronic obstructive pulmonary disease using whole-genome sequence data.Human molecular genetics · 2022Article
- Exome and Sputum Microbiota as Predictive Markers of Frequent Exacerbations in Chronic Obstructive Pulmonary Disease.Biomolecules · 2022Article
- Whole-Exome Sequencing of Bronchial Epithelial Cells Reveals a Genetic Print of Airway Remodelling in COPD.Biomedicines · 2022Article
- Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder.The Lancet. Respiratory medicine · 2022Review
- Identification of novel key genes associated with the metastasis of prostate cancer based on bioinformatics prediction and validation.Cancer cell international · 2021Article
- Whole-Exome Sequencing Implicates theFrontiers in cell and developmental biology · 2021Article
- Genetics of COPD.Annual review of physiology · 2020Review
- Genetic Advances in Chronic Obstructive Pulmonary Disease. Insights from COPDGene.American journal of respiratory and critical care medicine · 2019Review
- Initiating drug therapy in early stage chronic obstructive pulmonary disease: does it impact the course and outcome?Current opinion in pulmonary medicine · 2019Review
- High-Throughput Sequencing in Respiratory, Critical Care, and Sleep Medicine Research. An Official American Thoracic Society Workshop Report.Annals of the American Thoracic Society · 2019Article
- metaFARVAT: An Efficient Tool for Meta-Analysis of Family-Based, Case-Control, and Population-Based Rare Variant Association Studies.Frontiers in genetics · 2019Article
- Applying Functional Genomics to Chronic Obstructive Pulmonary Disease.Annals of the American Thoracic Society · 2018Review
- Whole exome sequencing analysis in severe chronic obstructive pulmonary disease.Human molecular genetics · 2018Article
- Whole-Genome Sequencing in Severe Chronic Obstructive Pulmonary Disease.American journal of respiratory cell and molecular biology · 2018Article
- RNAseq analysis of bronchial epithelial cells to identify COPD-associated genes and SNPs.BMC pulmonary medicine · 2018Article
- Whole-Transcriptome Sequencing: a Powerful Tool for Vascular Tissue Engineering and Endothelial Mechanobiology.High-throughput · 2018Review
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Authors and funding
18 authors at 8 institutions in 1 country.
Funding
Abstract
rationaleGenomic regions identified by genome-wide association studies explain only a small fraction of heritability for chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin deficiency shows that rare coding variants of large effect also influence COPD susceptibility. We hypothesized that exome sequencing in families identified through a proband with severe, early-onset COPD would identify additional rare genetic determinants of large effect.
objectivesTo identify rare genetic determinants of severe COPD.
methodsWe applied filtering approaches to identify potential causal variants for COPD in whole exomes from 347 subjects in 49 extended pedigrees from the Boston Early-Onset COPD Study. We assessed the power of this approach under different levels of genetic heterogeneity using simulations. We tested genes identified in these families using gene-based association tests in exomes of 204 cases with severe COPD and 195 resistant smokers from the COPDGene study. In addition, we examined previously described loci associated with COPD using these datasets. MEASUREMENTS AND MAIN
resultsWe identified 69 genes with predicted deleterious nonsynonymous, stop, or splice variants that segregated with severe COPD in at least two pedigrees. Four genes (DNAH8, ALCAM, RARS, and GBF1) also demonstrated an increase in rare nonsynonymous, stop, and/or splice mutations in cases compared with resistant smokers from the COPDGene study; however, these results were not statistically significant. We demonstrate the limitations of the power of this approach under genetic heterogeneity through simulation.
conclusionsRare deleterious coding variants may increase risk for COPD, but multiple genes likely contribute to COPD susceptibility.
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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.