ArticleNature genetics2014
A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations.
Registry-linked trialAbstract read
In one paragraph
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05365841 (Role of Epithelial Barrier Integrity in Biologic Treatment Response of Severe Asthmatics With/Out Chronic Rhinosinusitis With Nasal Polyps), which is not on this map. Cited by 300 papers, 8 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
300citing papers in PubMed, 8 pooled it
21.3field-weighted citation impact, top 1% of its field
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.
Role of Epithelial Barrier Integrity in Biologic Treatment Response of Severe Asthmatics With/Out Chronic Rhinosinusitis With Nasal Polyps (CRSwNP). Can Shedding of Epithelial Barrier Proteins be Used as Biomarker in Severe Asthma With/Out CRSwNP Management?
Who cites it
300 citing papers in PubMed, 8 syntheses or guidelines pooled it, 576 citations in OpenAlex.
- Genetic characterization of preschool wheeze phenotypes.The Journal of allergy and clinical immunology · 2025Pooled it
- 131 genetic loci highlight immunological pathways and tissues in nasal polyposis and asthma.Nature communications · 2025Pooled it
- A meta-analysis of genome-wide association studies of childhood wheezing phenotypes identifieseLife · 2023Pooled it
- Genetically high angiotensin-converting enzyme concentrations causally increase asthma risk: A meta-analysis using Mendelian randomization.Frontiers in medicine · 2022Pooled it
- The GSDMB rs7216389 SNP is associated with chronic rhinosinusitis in a multi-institutional cohort.International forum of allergy & rhinology · 2021Pooled it
- A genome-wide association study of severe asthma exacerbations in Latino children and adolescents.The European respiratory journal · 2021Pooled it
- Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis.Nature communications · 2020Pooled it
- Meta-analysis of airway epithelium gene expression in asthma.The European respiratory journal · 2018Pooled it
- Beyond RSV: why the bronchiolitis burden in infants will not simply disappear.European journal of pediatrics · 2026Review
- Pediatric and adult primary human airway epithelia exhibit similar rhinovirus C replication, innate responses, and expression of protein receptor.Microbiology spectrum · 2026Article
- Duration and severity of asthma-like episodes in young children vary by viral and bacterial triggers.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- Fungi in Asthma: From Epidemiology and Airway Mycobiome to Molecular Mechanisms and Novel Allergenic Phytopathogens.International journal of molecular sciences · 2026Review
- Associations Between Genetic Variants in the 17q21 Locus,Children (Basel, Switzerland) · 2026Article
- Interleukin-33 and its receptor: multifaceted roles and emerging therapeutic potential.Nature reviews. Immunology · 2026Review
- From Susceptibility to Severity: The Impact of Interleukin-33 rs1929992 Polymorphism on Asthma in a Taiwanese Population.Life (Basel, Switzerland) · 2026Article
- Rhinovirus Species in Acute Respiratory Tract Infections and the Risk of Asthma in Children.Pediatric pulmonology · 2026Article
- A robust cell-based infection model for Rhinovirus C research and antiviral drug discovery.Npj viruses · 2026Article
- Why Are Some Children More Sick Than Others? Lessons From Genome-wide Association Studies of Respiratory Viral Infections.The Pediatric infectious disease journal · 2026Article
- Multi-Ancestry Epigenome-Wide Meta-Analysis Identifies Novel Bulk and Cell-Type-Specific Epigenetic Markers of Asthma with Severe Exacerbations.medRxiv : the preprint server for health sciences · 2026Article
- Rhinovirus C15 infection induces airway epithelial cell remodeling and robust inflammatory responses: Potential implications for airway obstruction in children.Mucosal immunology · 2025Article
240 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
36 authors at 15 institutions in 5 countries.
Klaus Bønnelykke1] Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark. [2] [3].
Patrick Sleiman1] Center for Applied Genomics, Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. [2].
Kasper Nielsen1] Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark. [2].ORCID 0000000255107767
Eskil Kreiner-MøllerCopenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.ORCID 0000000312042438
Josep M MercaderJoint Institute for Research in Biomedicine and Barcelona Supercomputing Center (IRB-BSC) Program on Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain.
Danielle Belgrave1] Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, UK. [2] Centre for Health Informatics, Institute of Population Health, University of Manchester, Manchester, UK.
Herman T den Dekker1] Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands. [2] Department of Pediatrics, Division of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. [3] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Anders Husby1] Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark. [2] Brooke Laboratory, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK.
Astrid SevelstedCopenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
Grissel Faura-Tellez1] Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK. [2] Pediatric Pulmonology and Pediatric Allergology, University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands.
Li Juel MortensenCopenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
Lavinia PaternosterIntegrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, UK.
Richard FlaatenCopenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
Anne MølgaardCopenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
David E SmartBrooke Laboratory, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK.
Philip F ThomsenCenter for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
Morten A RasmussenDepartment of Food Science, University of Copenhagen, Copenhagen, Denmark.
Silvia Bonàs-GuarchJoint Institute for Research in Biomedicine and Barcelona Supercomputing Center (IRB-BSC) Program on Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain.
Claus HolstInstitute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
Ellen A Nohr1] Institute of Clinical Research, University of Southern Denmark, Aarhus, Denmark. [2] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
Rachita YadavCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
Michael E MarchCenter for Applied Genomics, Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA.
Thomas BlicherNovo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Peter M LackieFaculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
Vincent W V Jaddoe1] Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands. [2] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. [3] Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.
Angela SimpsonCentre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, UK.
John W HollowayFaculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
Liesbeth Duijts1] Department of Pediatrics, Division of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. [2] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. [3] Department of Pediatrics, Division of Neonatology, Erasmus Medical Center, Rotterdam, The Netherlands.
Adnan CustovicCentre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester, UK.
Donna E DaviesBrooke Laboratory, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK.
David Torrents1] Joint Institute for Research in Biomedicine and Barcelona Supercomputing Center (IRB-BSC) Program on Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain. [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Ramneek GuptaCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
Mads V HollegaardDanish Centre for Neonatal Screening, Department of Clinical Biochemistry and Immunology, Statens Serum Institut (SSI), Copenhagen, Denmark.
David M HougaardDanish Centre for Neonatal Screening, Department of Clinical Biochemistry and Immunology, Statens Serum Institut (SSI), Copenhagen, Denmark.
Hakon Hakonarson1] Center for Applied Genomics, Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA. [2].
Hans Bisgaard1] Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark. [2].
University of Copenhagen · DKChildren's Hospital of Philadelphia · USErasmus MC · NLTechnical University of Denmark · DKBarcelona Supercomputing Center · ESSouthampton General Hospital · GBStatens Serum Institut · DKUniversity Hospital Southampton NHS Foundation Trust · GBUniversity of Manchester · GBCopenhagen University Hospital · DKInstitució Catalana de Recerca i Estudis Avançats · ESManchester Academic Health Science Centre · GBUniversity Medical Center Groningen · NLUniversity of Bristol · GBUniversity of Southern Denmark · DK
Funding
Integrative Analysis of a GWAS Repository with EMRs from over 40,000 ChildrenU01HG006830 · NHGRI · CHILDREN'S HOSP OF PHILADELPHIA · PI HAKONARSON, HAKON · 2012 to 2014
$3.7MMedical Research Council G0501506Medical Research Council G0601361Medical Research Council G0900453Medical Research Council MR/K002449/1NHGRI NIH HHS U01 HG006830
Abstract
Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes.
Indexed as
Genetic Predisposition to DiseaseAcid Anhydride HydrolasesAsthmaCadherin Related ProteinsCadherinsCase-Control StudiesChildChild, PreschoolChromosomes, Human, Pair 17DenmarkDNA-Binding ProteinsDNA Repair EnzymesFemaleGasderminsGenome-Wide Association StudyHumansAcid Anhydride HydrolasesCadherin Related ProteinsCadherinsCDHR3 protein, humanDNA-Binding ProteinsDNA Repair EnzymesGasderminsGSDMB protein, humanIL1RL1 protein, humanIL33 protein, humanInterleukin-1 Receptor-Like 1 ProteinInterleukin-33InterleukinsMembrane ProteinsNeoplasm ProteinsRAD50 protein, humanReceptors, Cell Surface
Identifiers
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Registered trials
NCT05365841ClinicalTrials.gov
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.