Genome-wide meta-analysis implicates variation affecting mast cell biology in urticaria.
Urticaria
genome-wide association study
mast cells
meta-analysis
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
09 Sep 2023
09 Sep 2023
Historique:
received:
29
04
2023
revised:
13
08
2023
accepted:
31
08
2023
pubmed:
11
9
2023
medline:
11
9
2023
entrez:
10
9
2023
Statut:
aheadofprint
Résumé
Urticaria is characterized by inappropriate mast cell degranulation leading to the development of wheals and/or angioedema. Twin and family studies indicate that there is a substantial heritable component to urticaria risk. Our aim was to identify genomic loci at which common genetic variation influences urticaria susceptibility. Genome-wide association studies of urticaria (including all subtypes) from 3 European cohorts (UK Biobank, FinnGen, and the Trøndelag Health Study [HUNT]) were combined through statistical meta-analysis (14,306 urticaria cases and 650,664 controls). Cases were identified via electronic health care records from primary and/or secondary care. To identify putative causal variants and genes, statistical fine-mapping, colocalization, and interrogation of publicly available single-cell transcriptome sequencing resources were performed. Genome-wide significant associations (P < 5 × 10 Common genetic variation influencing the risk of developing urticaria was identified at 6 genomic loci. The relationship between genes with roles in mast cell biology and several association signals implicates genetic variability of specific components of mast cell function in the development of urticaria.
Sections du résumé
BACKGROUND
BACKGROUND
Urticaria is characterized by inappropriate mast cell degranulation leading to the development of wheals and/or angioedema. Twin and family studies indicate that there is a substantial heritable component to urticaria risk.
OBJECTIVE
OBJECTIVE
Our aim was to identify genomic loci at which common genetic variation influences urticaria susceptibility.
METHODS
METHODS
Genome-wide association studies of urticaria (including all subtypes) from 3 European cohorts (UK Biobank, FinnGen, and the Trøndelag Health Study [HUNT]) were combined through statistical meta-analysis (14,306 urticaria cases and 650,664 controls). Cases were identified via electronic health care records from primary and/or secondary care. To identify putative causal variants and genes, statistical fine-mapping, colocalization, and interrogation of publicly available single-cell transcriptome sequencing resources were performed.
RESULTS
RESULTS
Genome-wide significant associations (P < 5 × 10
CONCLUSION
CONCLUSIONS
Common genetic variation influencing the risk of developing urticaria was identified at 6 genomic loci. The relationship between genes with roles in mast cell biology and several association signals implicates genetic variability of specific components of mast cell function in the development of urticaria.
Identifiants
pubmed: 37690594
pii: S0091-6749(23)01117-X
doi: 10.1016/j.jaci.2023.08.033
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.