ArticleThe Lancet. Respiratory medicine2019
Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study.
Article in The Lancet. Respiratory medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 10 of them syntheses that pooled it.
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Who cites it
140 citing papers in PubMed, 10 syntheses or guidelines pooled it, 252 citations in OpenAlex.
- Assessing causal relationships between gut microbiota and asthma: evidence from two sample Mendelian randomization analysis.Frontiers in immunology · 2023Pooled it
- A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.Journal of medical Internet research · 2022Pooled it
- Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness.Scientific reports · 2022Pooled it
- Multi-ancestry genome-wide association study of asthma exacerbations.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2022Pooled it
- Pooled it
- Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease.Nature communications · 2021Pooled it
- Genome-wide search for genes affecting the age at diagnosis of type 1 diabetes.Journal of internal medicine · 2021Pooled it
- A genome-wide study of DNA methylation in white blood cells and asthma in Latino children and youth.Epigenetics · 2021Pooled it
- Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma.Nature communications · 2020Pooled it
- Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis.Nature communications · 2020Pooled it
- Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial.Lancet (London, England) · 2022Trial
- TET2 promotes monocyte inflammatory activation in asthma via ALKBH5-m6A regulation and PI3K signaling: evidence from m6A-SNP and single-cell analyses.Molecular genetics and genomics : MGG · 2026Article
- Post-genome-wide association study variant-to-function challenges in asthma research.The Journal of allergy and clinical immunology · 2026Review
- The Genetic Architecture of Chronic Cough: From Sensory Hypersensitivity to Treatable Trait.Pulmonary therapy · 2026Review
- Genome-wide association study of asthma with high treatment burden and/or worse outcomes defined using electronic healthcare data in UK Biobank.ERJ open research · 2026Article
- Role of miR-191-3p in HDM-induced airway epithelial inflammation by targeting CD247 in allergic asthma.BMC immunology · 2026Article
- Complex structural variation, phylogeny, and disease associations of the mucin pangenome.medRxiv : the preprint server for health sciences · 2026Article
- Cumulative genetic risk for asthma contributes to disease severity in children with asthma.The journal of allergy and clinical immunology. Global · 2026Article
- Rheumatoid arthritis and airway hyperresponsiveness: A GWAS-based mendelian randomization study.Medicine · 2026Article
- Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
43 authors at 19 institutions in 5 countries.
Funding
Abstract
backgroundFew genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel genetic variants associated with moderate-to-severe asthma, see whether previously identified genetic variants for all types of asthma contribute to moderate-to-severe asthma, and provide novel mechanistic insights using expression analyses in patients with asthma.
methodsIn this genome-wide association study, we used a two-stage case-control design. In stage 1, we genotyped patient-level data from two UK cohorts (the Genetics of Asthma Severity and Phenotypes [GASP] initiative and the Unbiased BIOmarkers in PREDiction of respiratory disease outcomes [U-BIOPRED] project) and used data from the UK Biobank to collect patient-level genomic data for cases and controls of European ancestry in a 1:5 ratio. Cases were defined as having moderate-to-severe asthma if they were taking appropriate medication or had been diagnosed by a doctor. Controls were defined as not having asthma, rhinitis, eczema, allergy, emphysema, or chronic bronchitis as diagnosed by a doctor. For stage 2, an independent cohort of cases and controls (1:5) was selected from the UK Biobank only, with no overlap with stage 1 samples. In stage 1 we undertook a genome-wide association study of moderate-to-severe asthma, and in stage 2 we followed up independent variants that reached the significance threshold of p less than 1 × 10
findingsWe included 5135 cases and 25 675 controls for stage 1, and 5414 cases and 21 471 controls for stage 2. We identified 24 genome-wide significant signals of association with moderate-to-severe asthma, including several signals in innate or adaptive immune-response genes. Three novel signals were identified: rs10905284 in GATA3 (coded allele A, odds ratio [OR] 0·90, 95% CI 0·88-0·93; p=1·76 × 10
interpretationWe found substantial shared genetic architecture between mild and moderate-to-severe asthma. We also report for the first time genetic variants associated with the risk of developing moderate-to-severe asthma that regulate mucin production. Finally, we identify candidate causal genes in these loci and provide increased insight into this difficult to treat population.
fundingAsthma UK, AirPROM, U-BIOPRED, UK Medical Research Council, and Rosetrees Trust.
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