Evidence map›Paper›PMID 40769318›Full record

SynthesisThe Journal of allergy and clinical immunology2025

Genetic characterization of preschool wheeze phenotypes.

Kasper Fischer-Rasmussen, Raquel Granell, Anders Ulrik Eliasen, Eskil Kreiner, Casper-Emil Tingskov Pedersen, Yang Luo, Bo Chawes, Jakob Stokholm, Ann-Marie Malby Schoos, Ashish Kumar and 44 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Journal of allergy and clinical immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

54 authors.

Kasper Fischer-RasmussenCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Raquel GranellMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Anders Ulrik EliasenCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Eskil KreinerCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Casper-Emil Tingskov PedersenCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Yang LuoCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Bo ChawesCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jakob StokholmCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Ann-Marie Malby SchoosCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Pediatrics, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark; Department of Pediatrics, Copenhagen University Hospital - Næstved, Slagelse and Ringsted, Slagelse, Denmark.
Ashish KumarDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Anne-Marie Nybo AndersenDepartment of Public Health, University of Copenhagen, Copenhagen, Denmark.
Bjarke FeenstraDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Frank GellerDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Valérie SirouxUniversité Paris Cité, INSERM, UMR 1124, Group of Genomic Epidemiology of Multifactorial Diseases, Paris, France.
Florence DemenaisUniversité Paris Cité, INSERM, UMR 1124, Group of Genomic Epidemiology of Multifactorial Diseases, Paris, France.
Emmanuelle BouzigonUniversité Paris Cité, INSERM, UMR 1124, Group of Genomic Epidemiology of Multifactorial Diseases, Paris, France.
Vincent JaddoeThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Ralf J P van der ValkThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Liesbeth DuijtsThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Jordi SunyerISGlobal, Barcelona, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Mónica GuxensISGlobal, Barcelona, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública, Madrid, Spain; ICREA, Barcelona, Spain.
Marcella MarinelliSpanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
Mariona BustamanteSpanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Joachim HeinrichDivision of Metabolic and Nutritional Medicine, Ludwig-Maximilians-Universitat (LMU) Munich, Dr von Hauner Children's Hospital, University of Munich Medical Center, Munich, Germany; Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Munich, Germany.
Marie StandlInstitute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Lung Research (DZL); German Center for Child and Adolescent Health (DZKJ), Munich, Germany.
John CurtinDivision of Immunology, Immunity to Infection and Respiratory Medicine, Manchester Academic Health Science Centre, School of Biological Sciences, University of Manchester, Manchester, United Kingdom; National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, Manchester University Hospital NHS Foundation Trust, Manchester, United Kingdom.
Angela SimpsonNational Institute for Health Research (NIHR) Manchester Biomedical Research Centre, Manchester University Hospital NHS Foundation Trust, Manchester, United Kingdom.
Clare MurrayNational Institute for Health Research (NIHR) Manchester Biomedical Research Centre, Manchester University Hospital NHS Foundation Trust, Manchester, United Kingdom.
Bo JacobssonDepartment of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway; Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg, Sweden.
Ronny MyhreDepartment of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway.
Craig E PennellHunter Medical Research Institute, New Lambton Heights, Australia; Mothers and Babies Research Centre and John Hunter Hospital, New Lambton Heights, Australia; School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, Australia.
Denise DaleyCenter for Heart and Lung Innovation, University of British Columbia, Vancouver, Canada; University of British Columbia, Faculty of Medicine, Vancouver, Canada.
Carole OberDepartment of Human Genetics, University of Chicago, Chicago, Ill.
James E GernDepartment of Medicine, University of British Columbia, Vancouver, Canada; Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wis.
Daniel JacksonDepartment of Medicine, University of British Columbia, Vancouver, Canada.
Dorret I BoomsmaDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Jouke-Jan HottengaDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Abdel AbdellaouiDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
John W HollowayNIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, The Netherlands; Human Development and Health, University of Southampton Faculty of Medicine, Southampton, The Netherlands.
Sam CollinsNIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, The Netherlands; Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, The Netherlands.
Stephen TurnerClinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, The Netherlands; Child Health, University of Aberdeen, Aberdeen, United Kingdom.
S Hasan ArshadNIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, The Netherlands; Human Development and Health, University of Southampton Faculty of Medicine, Southampton, The Netherlands; Women and Children Division, NHS Grampian, Aberdeen, United Kingdom.
Anhar UllahNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Erik MelénDepartment of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Sach's Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
John HendersonMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Hans BisgaardCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Anders Gorm PedersenDepartment of Health Technology, Section for Bioinformatics, Technical University of Denmark, Kongens Lyngby, Denmark.
Adnan CustovicPediatric Allergy, Imperial College London, London, United Kingdom.
Judith M VonkGroningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, Groningen, The Netherlands.
Gerard H KoppelmanGroningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, Groningen, The Netherlands; Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Michael KabeschDepartment of Pediatric Pneumology and Allergy, St Hedwig's Hospital of the Order of St John, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
Klaus BønnelykkeCopenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: kb@copsac.com.
Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community (GABRIEL) consortium
EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium

Funding

Mechanistic insights into asthma pathogenesis through the integration of asthma genes, risk exposures, and metabolomicsR01HL141826 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LASKY-SU, JESSICA A · 2018 to 2021
$3.4M
Prenatal Origins of AsthmaR01HL129735 · NHLBI · UNIVERSITY OF CHICAGO · PI BISGAARD, HANS, OBER, CAROLE · 2015 to 2018
$3.2M
NHLBI NIH HHS R01 HL129735NHLBI NIH HHS R01 HL141826
6 · The paper itself

Abstract

backgroundPreschool wheeze is a heterogenous and poorly understood clinical syndrome. As a result, current treatments are insufficient, and prevention is not possible.

objectiveWe sought to increase understanding of the genetic susceptibility and underlying disease mechanisms of wheeze phenotypes in early childhood through large-scale genome-wide association study analyses.

methodsWe performed meta-analyses of genome-wide association study on early-onset wheeze, defined as recurrent wheeze or asthma in the first 3 years of life, and its subtypes, including early transient and persistent wheeze, defined by asthma/wheeze at age 3 and subsequent remission or persistence at age 6, respectively. The discovery analyses included data on more than 13,000 children from 15 cohorts; replication was sought through meta-analyses of data from 7 additional cohorts including up to 5000 children. Genetic variants associated with asthma-related traits in adulthood (adult asthma, atopy, eosinophils, and lung function) were used to quantify the degree to which genetic risk influencing asthma-related adult traits also influences genetic risk of preschool wheeze.

resultsVariants near the GSDMB gene in the 17q region showed genome-wide significant association with early-onset wheeze (rs2305480; odds ratio [95% confidence interval] = 1.26 [1.17-1.33], P = 2.30E-16) and persistent wheeze (rs11078926; 1.43 [1.30-1.578], P = 2.14E-11), but not with early transient wheeze (rs1054609; 1.08 [0.98-1.18], P = .094). Other known asthma loci were associated with early-onset wheeze, particularly CDHR3. Additionally, increased genetic risk to early-onset wheeze was associated with genetic risk for asthma at older ages, atopy, eosinophil count, and lower adult lung function. This was driven by persistent wheeze, whereas transient early wheeze was only associated with low lung function.

conclusionsPreschool wheeze phenotypes displayed distinct patterns of single nucleotide polymorphism associations and genetic enrichment with asthma-related traits. These results indicate distinct etiologies of wheeze phenotypes, which could inform studies in optimization of prevention and treatment strategies.

Indexed as

AsthmaRespiratory SoundsChildChild, PreschoolFemaleGasderminsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInfantMalePhenotypePolymorphism, Single NucleotideGasderminsGSDMB protein, human17q21-12asthma comorbiditiesgenetic overlapgenome-wide association studyPreschool wheeze

Identifiers

PMID40769318
PMCPMC13592397

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.