Phenotype wide association study links bronchopulmonary dysplasia with eosinophilia in children.
Humans
Bronchopulmonary Dysplasia
/ genetics
Polymorphism, Single Nucleotide
Male
Female
Eosinophilia
/ genetics
Child
Phenotype
Asthma
/ genetics
Interleukin-1 Receptor-Like 1 Protein
/ genetics
Genetic Predisposition to Disease
Infant, Newborn
Genome-Wide Association Study
Child, Preschool
DNA Methylation
Infant
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 Sep 2024
13 Sep 2024
Historique:
received:
02
02
2024
accepted:
05
09
2024
medline:
14
9
2024
pubmed:
14
9
2024
entrez:
13
9
2024
Statut:
epublish
Résumé
Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Despite this, genetic drivers of BPD are poorly understood. The objective of this study is to better understand the impact of single nucleotide polymorphisms (SNPs) previously associated with BPD by examining associations with other phenotypes. We drew pediatric subjects from the biorepository at the Center for Applied Genomics to identify associations between these SNPs and 2,146 imputed phenotypes. Methylation data, external cohorts, and in silico validation methods were used to corroborate significant associations. We identified 60 SNPs that were previously associated with BPD. We found a significant association between rs3771150 and rs3771171 and mean eosinophil percentage in a European cohort of 6,999 patients and replicated this in external cohorts. Both SNPs were also associated with asthma, COPD and FEV1/FVC ratio. These SNPs displayed associations with methylation probes and were functionally linked to ST2 (IL1RL1) levels in blood and lung tissue. Our findings support a genetic justification for the epidemiological link between BPD and asthma. Given the well-established link between ST2 and type 2 inflammation in asthma, these findings provide a rationale for future studies exploring the role of type 2 inflammation in the pathogenesis of BPD.
Identifiants
pubmed: 39271728
doi: 10.1038/s41598-024-72348-5
pii: 10.1038/s41598-024-72348-5
doi:
Substances chimiques
Interleukin-1 Receptor-Like 1 Protein
0
IL1RL1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21391Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Informations de copyright
© 2024. The Author(s).
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