ArticlePloS one2014
Whole-genome sequencing of individuals from a founder population identifies candidate genes for asthma.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Exploring the role of protein homeostasis regulation in glycolysis in head and neck tumors.Human cell · 2026Review
- The Ubiquitin-Proteasome System in Asthma: Mechanisms and Therapeutic Possibilities.Clinical reviews in allergy & immunology · 2025Review
- Copy Number Variation in Asthma: An Integrative Review.Clinical reviews in allergy & immunology · 2025Review
- Asthma-Genomic Advances Toward Risk Prediction.Clinics in chest medicine · 2024Review
- Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma.The Journal of allergy and clinical immunology · 2024Article
- NEDD4L inhibits glycolysis and proliferation of cancer cells in oral squamous cell carcinoma by inducing ENO1 ubiquitination and degradation.Cancer biology & therapy · 2022Article
- Review
- Multi-Omics Profiling Approach to Asthma: An Evolving Paradigm.Journal of personalized medicine · 2022Review
- Genetics and Epigenetics in Asthma.International journal of molecular sciences · 2021Review
- The effects of genotype × phenotype interactions on silver nanoparticle toxicity in organotypic cultures of murine tracheal epithelial cells.Nanotoxicology · 2020Article
- Targeting defective sphingosine kinase 1 in Niemann-Pick type C disease with an activator mitigates cholesterol accumulation.The Journal of biological chemistry · 2020Article
- Pharmacogenetics of Pediatric Asthma: Current Perspectives.Pharmacogenomics and personalized medicine · 2020Review
- Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma.Chest · 2019Article
- Diagnostic Yields of Trio-WES Accompanied by CNVseq for Rare Neurodevelopmental Disorders.Frontiers in genetics · 2019Article
- Genomic Predictors of Asthma Phenotypes and Treatment Response.Frontiers in pediatrics · 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
- The Cell Research Trends of Asthma: A Stem Frequency Analysis of the Literature.Journal of healthcare engineering · 2018Article
- Whole-Genome Sequencing in Common Respiratory Diseases. Ready, Set, Go!American journal of respiratory and critical care medicine · 2017Article
- Patient complexity and genotype-phenotype correlations in biliary atresia: a cross-sectional analysis.BMC medical genomics · 2017Article
- The puzzle of immune phenotypes of childhood asthma.Molecular and cellular pediatrics · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 8 institutions in 2 countries.
Funding
Abstract
Asthma is a complex genetic disease caused by a combination of genetic and environmental risk factors. We sought to test classes of genetic variants largely missed by genome-wide association studies (GWAS), including copy number variants (CNVs) and low-frequency variants, by performing whole-genome sequencing (WGS) on 16 individuals from asthma-enriched and asthma-depleted families. The samples were obtained from an extended 13-generation Hutterite pedigree with reduced genetic heterogeneity due to a small founding gene pool and reduced environmental heterogeneity as a result of a communal lifestyle. We sequenced each individual to an average depth of 13-fold, generated a comprehensive catalog of genetic variants, and tested the most severe mutations for association with asthma. We identified and validated 1960 CNVs, 19 nonsense or splice-site single nucleotide variants (SNVs), and 18 insertions or deletions that were out of frame. As follow-up, we performed targeted sequencing of 16 genes in 837 cases and 540 controls of Puerto Rican ancestry and found that controls carry a significantly higher burden of mutations in IL27RA (2.0% of controls; 0.23% of cases; nominal p = 0.004; Bonferroni p = 0.21). We also genotyped 593 CNVs in 1199 Hutterite individuals. We identified a nominally significant association (p = 0.03; Odds ratio (OR) = 3.13) between a 6 kbp deletion in an intron of NEDD4L and increased risk of asthma. We genotyped this deletion in an additional 4787 non-Hutterite individuals (nominal p = 0.056; OR = 1.69). NEDD4L is expressed in bronchial epithelial cells, and conditional knockout of this gene in the lung in mice leads to severe inflammation and mucus accumulation. Our study represents one of the early instances of applying WGS to complex disease with a large environmental component and demonstrates how WGS can identify risk variants, including CNVs and low-frequency variants, largely untested in GWAS.
Indexed as
Identifiers
What Socratic holds
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.