ArticleClinical and translational allergy2023
Association of asthma genetic variants with asthma-associated traits reveals molecular pathways of eosinophilic asthma.
Article in Clinical and translational allergy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 19 citations in OpenAlex.
- Family-based genome-wide association study for asthma among Han Chinese children.BMC pediatrics · 2026Article
- Asthma-Genomic Advances Toward Risk Prediction.Clinics in chest medicine · 2024Review
- CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.International journal of molecular sciences · 2024Review
- Pulmonary function in swimmers exposed to disinfection by-products: a narrative review.Frontiers in physiology · 2024Review
- Novel insights into the whole-blood DNA methylome of asthma in ethnically diverse children and youth.The European respiratory journal · 2023Article
- Article
- Association of asthma genetic variants with asthma-associated traits reveals molecular pathways of eosinophilic asthma.Clinical and translational allergy · 2023Article
- Interactions between calcium regulatory pathways and mechanosensitive channels in airways.Expert review of respiratory medicineReview
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
introductionAsthma is a complex, polygenic, heterogenous inflammatory disease. Recently, we generated a list of 128 independent single nucleotide polymorphisms (SNPs) associated with asthma in genome-wide association studies. However, it is unknown if asthma SNPs are associated with specific asthma-associated traits such as high eosinophil counts, atopy, and airway obstruction, revealing molecular endotypes of this disease. Here, we aim to identify the association between asthma SNPs and asthma-associated traits and assess expression quantitative trait locus (e-QTLs) to reveal their downstream functional effects and find drug targets.
methodsAssociation analyses between 128 asthma SNPs and associated traits (blood eosinophil numbers, atopy, airway obstruction, airway hyperresponsiveness) were conducted using regression modelling in population-based studies (Lifelines N = 32,817/Vlagtwedde-Vlaardingen N = 1554) and an asthma cohort (Dutch Asthma genome-wide association study N = 917). Functional enrichment and pathway analysis were performed with genes linked to the significant SNPs by e-QTL analysis. Genes were investigated to generate novel drug targets.
resultsWe identified 69 asthma SNPs that were associated with at least one trait, with 20 SNPs being associated with multiple traits. The SNP annotated to SMAD3 was the most pleiotropic. In total, 42 SNPs were associated with eosinophil counts, 18 SNPs with airway obstruction, and 21 SNPs with atopy. We identified genetically driven pathways regulating eosinophilia. The largest network of eosinophilia contained two genes (IL4R, TSLP) targeted by drugs currently available for eosinophilic asthma. Several novel targets were identified such as IL-18, CCR4, and calcineurin.
conclusionMany asthma SNPs are associated with blood eosinophil counts and genetically driven molecular pathways of asthma-associated traits were identified.
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