Asthma exacerbations and eosinophilia in the UK Biobank: a genome-wide association study.


Journal

ERJ open research
ISSN: 2312-0541
Titre abrégé: ERJ Open Res
Pays: England
ID NLM: 101671641

Informations de publication

Date de publication:
Jan 2024
Historique:
received: 04 08 2023
accepted: 31 10 2023
medline: 10 1 2024
pubmed: 10 1 2024
entrez: 10 1 2024
Statut: epublish

Résumé

Asthma exacerbations reflect disease severity, affect morbidity and mortality, and may lead to declining lung function. Inflammatory endotypes ( UK Biobank data were used to perform a genome-wide association study of individuals with asthma and at least one exacerbation compared to individuals with asthma and no history of exacerbations. Individuals with asthma were identified using self-reported data, hospitalisation data and general practitioner records. Exacerbations were identified as either asthma-related hospitalisation, general practitioner record of asthma exacerbation or an oral corticosteroid burst prescription. A logistic regression model adjusted for age, sex, smoking status and genetic ancestry In the UK Biobank, we identified 11 604 cases and 37 890 controls. While no variants reached genome-wide significance (p<5×10 Our study has identified reproducible associations with asthma exacerbations in the UK Biobank and GERA cohorts. Confirmation of these findings in different asthma subphenotypes in diverse ancestries and functional investigation will be required to understand their mechanisms of action and potentially inform therapeutic development.

Sections du résumé

Background UNASSIGNED
Asthma exacerbations reflect disease severity, affect morbidity and mortality, and may lead to declining lung function. Inflammatory endotypes (
Methods UNASSIGNED
UK Biobank data were used to perform a genome-wide association study of individuals with asthma and at least one exacerbation compared to individuals with asthma and no history of exacerbations. Individuals with asthma were identified using self-reported data, hospitalisation data and general practitioner records. Exacerbations were identified as either asthma-related hospitalisation, general practitioner record of asthma exacerbation or an oral corticosteroid burst prescription. A logistic regression model adjusted for age, sex, smoking status and genetic ancestry
Results UNASSIGNED
In the UK Biobank, we identified 11 604 cases and 37 890 controls. While no variants reached genome-wide significance (p<5×10
Conclusions UNASSIGNED
Our study has identified reproducible associations with asthma exacerbations in the UK Biobank and GERA cohorts. Confirmation of these findings in different asthma subphenotypes in diverse ancestries and functional investigation will be required to understand their mechanisms of action and potentially inform therapeutic development.

Identifiants

pubmed: 38196893
doi: 10.1183/23120541.00566-2023
pii: 00566-2023
pmc: PMC10772900
pii:
doi:

Types de publication

Journal Article

Langues

eng

Informations de copyright

Copyright ©The authors 2024.

Déclaration de conflit d'intérêts

Conflict of interest: M. Tobin received funding from Orion Pharma and GSK, outside the submitted work. Conflict of interest: L. Lahousse received consulting from AstraZeneca, and honoraria from IPSA vzw and Chiesi, all outside the submitted work; and is a leading member of the European and Belgian Respiratory Societies. Conflict of interest: A. Edris, K. Voorhies, A.C. Wu, S.M. Lutz, I. Hall, C. Iribarren and K. Fawcett declare no conflict of interest.

Auteurs

Ahmed Edris (A)

Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.

Kirsten Voorhies (K)

Precision Medicine Translational Research Center, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Sharon M Lutz (SM)

Precision Medicine Translational Research Center, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Carlos Iribarren (C)

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Ian Hall (I)

Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK.

Ann Chen Wu (AC)

Precision Medicine Translational Research Center, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Martin Tobin (M)

Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.

Katherine Fawcett (K)

Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK.
These authors contributed equally.

Lies Lahousse (L)

Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
These authors contributed equally.

Classifications MeSH