ArticleThe Journal of allergy and clinical immunology2024
Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma.
Article in The Journal of allergy and clinical immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Meta-evolutionary exome analysis identifies novel type 2 diabetes mellitus genes in the UK Biobank and all of us.PLoS genetics · 2025Pooled it
- Scientific Advances from Sharing URECA Data in Collaborative Analyses.The Journal of allergy and clinical immunology · 2026Review
- Associations between genetic ancestry and allergic outcomes at 10 years among Black children.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2026Article
- Cumulative genetic risk for asthma contributes to disease severity in children with asthma.The journal of allergy and clinical immunology. Global · 2026Article
- Mendelian randomization analysis of the causal relationship between plasma proteins and childhood asthma.Medicine · 2025Article
- Identifying Lipid Metabolism-Related Therapeutic Targets and Diagnostic Markers for Lung Adenocarcinoma by Mendelian Randomization and Machine Learning Analysis.Thoracic cancer · 2025Article
- Identification of Novel Biomarkers Associated with Corticosteroid Resistance in Asthma by Bioinformatics Analysis and Experimental Validation.Journal of inflammation research · 2025Article
Corrections and comments
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Authors and funding
27 authors at 18 institutions in 1 country.
Funding
Abstract
backgroundMost genetic studies of asthma and allergy have focused on common variation in individuals primarily of European ancestry. Studying the role of rare variation in quantitative phenotypes and in asthma phenotypes in populations of diverse ancestries can provide additional, important insights into the development of these traits.
objectiveWe sought to examine the contribution of rare variants to different asthma- or allergy-associated quantitative traits in children with diverse ancestries and explore their role in asthma phenotypes.
methodsWe examined whole-genome sequencing data from children participants in longitudinal studies of asthma (n = 1035; parent-identified as 67% Black and 25% Hispanic) to identify rare variants (minor allele frequency < 0.01). We assigned variants to genes and tested for associations using an omnibus variant-set test between each of 24,902 genes and 8 asthma-associated quantitative traits. On combining our results with external data on predicted gene expression in humans and mouse knockout studies, we identified 3 candidate genes. A burden of rare variants in each gene and in a combined 3-gene score was tested for its associations with clinical phenotypes of asthma. Finally, published single-cell gene expression data in lower airway mucosal cells after allergen challenge were used to assess transcriptional responses to allergen.
resultsRare variants in USF1 were significantly associated with blood neutrophil count (P = 2.18 × 10
conclusionsWe report novel associations between rare variants in genes and allergic and inflammatory phenotypes in children with diverse ancestries, highlighting TNFRSF21 as contributing to the development of allergic asthma.
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