-
Tytuł:
-
Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB.
-
Autorzy:
-
Eliasen AU; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, Kongens Lyngby, Denmark.
Pedersen CET; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Rasmussen MA; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Wang N; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Soverini M; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Fritz A; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, Kongens Lyngby, Denmark.
Stokholm J; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Chawes BL; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Morin A; Department of Human Genetics, University of Chicago, Chicago, Ill.
Bork-Jensen J; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Copenhagen, Denmark.
Grarup N; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Copenhagen, Denmark.
Pedersen O; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Copenhagen, Denmark.
Hansen T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Copenhagen, Denmark.
Linneberg A; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Mortensen PB; iPSYCH, The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark; National Center for Register-Based Research (NCRR), Business and Social Sciences, Aarhus University, Aarhus, Denmark; Center for Integrated Register-Based Research (CIRRAU), Aarhus University, Aarhus, Denmark.
Hougaard DM; iPSYCH, The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark; Department for Congenital Disorders, Statens Serum Institut (SSI), Copenhagen, Denmark; Den Neonatale Screenings Biobank, SSI, Copenhagen, Denmark.
Bybjerg-Grauholm J; iPSYCH, The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark; Den Neonatale Screenings Biobank, SSI, Copenhagen, Denmark.
Bækvad-Hansen M; iPSYCH, The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark; Department for Congenital Disorders, Statens Serum Institut (SSI), Copenhagen, Denmark.
Mors O; iPSYCH, The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark; Psychosis Research Unit, Aarhus University Hospital-Psychiatry, Risskov, Denmark.
Nordentoft M; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark; Mental Health Center Copenhagen, Capital Region of Denmark, Copenhagen University Hospital, Copenhagen, Denmark.
Børglum AD; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark; Center for Integrative Sequencing, Department of Biomedicine and iSEQ, Aarhus University, Aarhus, Denmark.
Werge T; iPSYCH, The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark; Institute of Biological Psychiatry, Copenhagen Mental Health Services, Copenhagen, Denmark; Institute of Clinical Medicine and GLOBE Institute, University of Copenhagen, Copenhagen, Denmark.
Agerbo E; iPSYCH, The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus, Denmark; National Center for Register-Based Research (NCRR), Business and Social Sciences, Aarhus University, Aarhus, Denmark; Center for Integrated Register-Based Research (CIRRAU), Aarhus University, Aarhus, Denmark.
Söderhall C; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Wash.
Altman MC; Department of Medicine, University of Washington, Seattle, Sweden.
Thysen AH; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
McKennan CG; Department of Statistics, University of Pittsburgh, Pittsburgh, Pa.
Brix S; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
Gern JE; Department of Pediatrics, University of Wisconsin, Madison, Wis.
Ober C; Department of Human Genetics, University of Chicago, Chicago, Ill.
Ahluwalia TS; Steno Diabetes Center Copenhagen, Gentofte, Denmark; Bioinformatics Center, University of Copenhagen, Copenhagen, Denmark.
Bisgaard H; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Pedersen AG; Department of Health Technology, Section for Bioinformatics, Technical University of Denmark, Kongens Lyngby, Denmark.
Bønnelykke K; Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: .
-
Źródło:
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2022 Sep; Vol. 150 (3), pp. 622-630. Date of Electronic Publication: 2022 Apr 02.
-
Typ publikacji:
-
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Original Publication: St Louis, Mosby.
-
MeSH Terms:
-
Asthma*/genetics
Genome-Wide Association Study*
Cadherin Related Proteins ; Cadherins/genetics ; Genetic Predisposition to Disease ; Humans ; Interleukin-17/genetics ; Membrane Proteins/genetics ; Neoplasm Proteins/genetics ; Polymorphism, Single Nucleotide ; Pore Forming Cytotoxic Proteins
-
Grant Information:
-
MC_PC_17228 United Kingdom MRC_ Medical Research Council; MC_QA137853 United Kingdom MRC_ Medical Research Council
-
Contributed Indexing:
-
Keywords: Childhood asthma; early life; genetic interactions; immunology
-
Substance Nomenclature:
-
0 (CDHR3 protein, human)
0 (Cadherin Related Proteins)
0 (Cadherins)
0 (GSDMB protein, human)
0 (Interleukin-17)
0 (Membrane Proteins)
0 (Neoplasm Proteins)
0 (Pore Forming Cytotoxic Proteins)
-
Entry Date(s):
-
Date Created: 20220405 Date Completed: 20220913 Latest Revision: 20230308
-
Update Code:
-
20240105
-
DOI:
-
10.1016/j.jaci.2022.03.019
-
PMID:
-
35381269
-
Background: Asthma with severe exacerbation is one of the most common causes of hospitalization among young children. Exacerbations are typically triggered by respiratory infections, but the host factors causing recurrent infections and exacerbations in some children are poorly understood. As a result, current treatment options and preventive measures are inadequate.
Objective: We sought to identify genetic interaction associated with the development of childhood asthma.
Methods: We performed an exhaustive search for pairwise interaction between genetic single nucleotide polymorphisms using 1204 cases of a specific phenotype of early childhood asthma with severe exacerbations in patients aged 2 to 6 years combined with 5328 nonasthmatic controls. Replication was attempted in 3 independent populations, and potential underlying immune mechanisms were investigated in the COPSAC2010 and COPSAC2000 birth cohorts.
Results: We found evidence of interaction, including replication in independent populations, between the known childhood asthma loci CDHR3 and GSDMB. The effect of CDHR3 was dependent on the GSDMB genotype, and this interaction was more pronounced for severe and early onset of disease. Blood immune analyses suggested a mechanism related to increased IL-17A production after viral stimulation.
Conclusions: We found evidence of interaction between CDHR3 and GSDMB in development of early childhood asthma, possibly related to increased IL-17A response to viral infections. This study demonstrates the importance of focusing on specific disease subtypes for understanding the genetic mechanisms of asthma.
(Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
