ArticleHuman molecular genetics2018
Whole exome sequencing analysis in severe chronic obstructive pulmonary disease.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Pooled it
- Genetic variants in pulmonary hypertension associated with chronic obstructive pulmonary disease.Current opinion in pulmonary medicine · 2026Review
- Airway ciliated cells in adult lung homeostasis and COPD.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Inference of chronic obstructive pulmonary disease with deep learning on raw spirograms identifies new genetic loci and improves risk models.Nature genetics · 2023Article
- Autoimmune Neutropenia and Immune-Dysregulation in a Patient Carrying aInternational journal of molecular sciences · 2022Article
- Assessing the contribution of rare genetic variants to phenotypes of chronic obstructive pulmonary disease using whole-genome sequence data.Human molecular genetics · 2022Article
- Whole-Exome Sequencing of Bronchial Epithelial Cells Reveals a Genetic Print of Airway Remodelling in COPD.Biomedicines · 2022Article
- Article
- Protein interaction networks define the genetic architecture of preterm birth.Scientific reports · 2022Article
- CiliOPD: a ciliopathy-associated COPD endotype.Respiratory research · 2021Article
- Mild catalytic defects of tert rs61748181 polymorphism affect the clinical presentation of chronic obstructive pulmonary disease.Scientific reports · 2021Article
- Reliability of genomic variants across different next-generation sequencing platforms and bioinformatic processing pipelines.BMC genomics · 2021Observational
- Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.Nature communications · 2020Article
- Scalability and cost-effectiveness analysis of whole genome-wide association studies on Google Cloud Platform and Amazon Web Services.Journal of the American Medical Informatics Association : JAMIA · 2020Article
- Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts.The Lancet. Respiratory medicine · 2020Article
- Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nature genetics · 2019Article
- Neoantigens in Chronic Obstructive Pulmonary Disease and Lung Cancer: A Point of View.Proteomics. Clinical applications · 2019Review
- Genomic Predictors of Asthma Phenotypes and Treatment Response.Frontiers in pediatrics · 2019Review
Corrections and comments
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Authors and funding
32 authors at 18 institutions in 6 countries.
Funding
Abstract
Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, is substantially influenced by genetic factors. Alpha-1 antitrypsin deficiency demonstrates that rare coding variants of large effect can influence COPD susceptibility. To identify additional rare coding variants in patients with severe COPD, we conducted whole exome sequencing analysis in 2543 subjects from two family-based studies (Boston Early-Onset COPD Study and International COPD Genetics Network) and one case-control study (COPDGene). Applying a gene-based segregation test in the family-based data, we identified significant segregation of rare loss of function variants in TBC1D10A and RFPL1 (P-value < 2x10-6), but were unable to find similar variants in the case-control study. In single-variant, gene-based and pathway association analyses, we were unable to find significant findings that replicated or were significant in meta-analysis. However, we found that the top results in the two datasets were in proximity to each other in the protein-protein interaction network (P-value = 0.014), suggesting enrichment of these results for similar biological processes. A network of these association results and their neighbors was significantly enriched in the transforming growth factor beta-receptor binding and cilia-related pathways. Finally, in a more detailed examination of candidate genes, we identified individuals with putative high-risk variants, including patients harboring homozygous mutations in genes associated with cutis laxa and Niemann-Pick Disease Type C. Our results likely reflect heterogeneity of genetic risk for COPD along with limitations of statistical power and functional annotation, and highlight the potential of network analysis to gain insight into genetic association studies.
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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 Socratic graph.