Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB

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Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB. / Eliasen, Anders U.; Pedersen, Casper Emil T.; Rasmussen, Morten A.; Wang, Ni; Soverini, Matteo; Fritz, Amelie; Stokholm, Jakob; Chawes, Bo L.; Morin, Andréanne; Bork-Jensen, Jette; Grarup, Niels; Pedersen, Oluf; Hansen, Torben; Linneberg, Allan; Mortensen, Preben B.; Hougaard, David M.; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Mors, Ole; Nordentoft, Merete; Børglum, Anders D.; Werge, Thomas; Agerbo, Esben; Söderhall, Cilla; Altman, Matthew C.; Thysen, Anna H.; McKennan, Chris G.; Brix, Susanne; Gern, James E.; Ober, Carole; Ahluwalia, Tarunveer S.; Bisgaard, Hans; Pedersen, Anders G.; Bønnelykke, Klaus.

I: Journal of Allergy and Clinical Immunology, Bind 150, Nr. 3, 2022, s. 622-630.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Eliasen, AU, Pedersen, CET, Rasmussen, MA, Wang, N, Soverini, M, Fritz, A, Stokholm, J, Chawes, BL, Morin, A, Bork-Jensen, J, Grarup, N, Pedersen, O, Hansen, T, Linneberg, A, Mortensen, PB, Hougaard, DM, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Mors, O, Nordentoft, M, Børglum, AD, Werge, T, Agerbo, E, Söderhall, C, Altman, MC, Thysen, AH, McKennan, CG, Brix, S, Gern, JE, Ober, C, Ahluwalia, TS, Bisgaard, H, Pedersen, AG & Bønnelykke, K 2022, 'Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB', Journal of Allergy and Clinical Immunology, bind 150, nr. 3, s. 622-630. https://doi.org/10.1016/j.jaci.2022.03.019

APA

Eliasen, A. U., Pedersen, C. E. T., Rasmussen, M. A., Wang, N., Soverini, M., Fritz, A., Stokholm, J., Chawes, B. L., Morin, A., Bork-Jensen, J., Grarup, N., Pedersen, O., Hansen, T., Linneberg, A., Mortensen, P. B., Hougaard, D. M., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Mors, O., ... Bønnelykke, K. (2022). Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB. Journal of Allergy and Clinical Immunology, 150(3), 622-630. https://doi.org/10.1016/j.jaci.2022.03.019

Vancouver

Eliasen AU, Pedersen CET, Rasmussen MA, Wang N, Soverini M, Fritz A o.a. Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB. Journal of Allergy and Clinical Immunology. 2022;150(3):622-630. https://doi.org/10.1016/j.jaci.2022.03.019

Author

Eliasen, Anders U. ; Pedersen, Casper Emil T. ; Rasmussen, Morten A. ; Wang, Ni ; Soverini, Matteo ; Fritz, Amelie ; Stokholm, Jakob ; Chawes, Bo L. ; Morin, Andréanne ; Bork-Jensen, Jette ; Grarup, Niels ; Pedersen, Oluf ; Hansen, Torben ; Linneberg, Allan ; Mortensen, Preben B. ; Hougaard, David M. ; Bybjerg-Grauholm, Jonas ; Bækvad-Hansen, Marie ; Mors, Ole ; Nordentoft, Merete ; Børglum, Anders D. ; Werge, Thomas ; Agerbo, Esben ; Söderhall, Cilla ; Altman, Matthew C. ; Thysen, Anna H. ; McKennan, Chris G. ; Brix, Susanne ; Gern, James E. ; Ober, Carole ; Ahluwalia, Tarunveer S. ; Bisgaard, Hans ; Pedersen, Anders G. ; Bønnelykke, Klaus. / Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB. I: Journal of Allergy and Clinical Immunology. 2022 ; Bind 150, Nr. 3. s. 622-630.

Bibtex

@article{19457530215f42219dfedc62d6ef831c,
title = "Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB",
abstract = "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.",
keywords = "Childhood asthma, early life, genetic interactions, immunology",
author = "Eliasen, {Anders U.} and Pedersen, {Casper Emil T.} and Rasmussen, {Morten A.} and Ni Wang and Matteo Soverini and Amelie Fritz and Jakob Stokholm and Chawes, {Bo L.} and Andr{\'e}anne Morin and Jette Bork-Jensen and Niels Grarup and Oluf Pedersen and Torben Hansen and Allan Linneberg and Mortensen, {Preben B.} and Hougaard, {David M.} and Jonas Bybjerg-Grauholm and Marie B{\ae}kvad-Hansen and Ole Mors and Merete Nordentoft and B{\o}rglum, {Anders D.} and Thomas Werge and Esben Agerbo and Cilla S{\"o}derhall and Altman, {Matthew C.} and Thysen, {Anna H.} and McKennan, {Chris G.} and Susanne Brix and Gern, {James E.} and Carole Ober and Ahluwalia, {Tarunveer S.} and Hans Bisgaard and Pedersen, {Anders G.} and Klaus B{\o}nnelykke",
note = "Publisher Copyright: {\textcopyright} 2022 American Academy of Allergy, Asthma & Immunology",
year = "2022",
doi = "10.1016/j.jaci.2022.03.019",
language = "English",
volume = "150",
pages = "622--630",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB

AU - Eliasen, Anders U.

AU - Pedersen, Casper Emil T.

AU - Rasmussen, Morten A.

AU - Wang, Ni

AU - Soverini, Matteo

AU - Fritz, Amelie

AU - Stokholm, Jakob

AU - Chawes, Bo L.

AU - Morin, Andréanne

AU - Bork-Jensen, Jette

AU - Grarup, Niels

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Linneberg, Allan

AU - Mortensen, Preben B.

AU - Hougaard, David M.

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Børglum, Anders D.

AU - Werge, Thomas

AU - Agerbo, Esben

AU - Söderhall, Cilla

AU - Altman, Matthew C.

AU - Thysen, Anna H.

AU - McKennan, Chris G.

AU - Brix, Susanne

AU - Gern, James E.

AU - Ober, Carole

AU - Ahluwalia, Tarunveer S.

AU - Bisgaard, Hans

AU - Pedersen, Anders G.

AU - Bønnelykke, Klaus

N1 - Publisher Copyright: © 2022 American Academy of Allergy, Asthma & Immunology

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Childhood asthma

KW - early life

KW - genetic interactions

KW - immunology

U2 - 10.1016/j.jaci.2022.03.019

DO - 10.1016/j.jaci.2022.03.019

M3 - Journal article

C2 - 35381269

AN - SCOPUS:85130353932

VL - 150

SP - 622

EP - 630

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -

ID: 308125958