ArticleThe Lancet. Respiratory medicine2013
Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study.
Article in The Lancet. Respiratory medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Personalized respiratory medicine: exploring the horizon, addressing the issues. Summary of a BRN-AJRCCM workshop held in Barcelona on June 12, 2014.American journal of respiratory and critical care medicine · 2015Pooled it
- Reduced mouse allergen is associated with epigenetic changes in regulatory genes, but not mouse sensitization, in asthmatic children.Environmental research · 2017Trial
- Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Cumulative genetic risk for asthma contributes to disease severity in children with asthma.The journal of allergy and clinical immunology. Global · 2026Article
- Potential Determinants of Progression from Cough-Variant Asthma to Classic Asthma in Children: Evidence, Mechanisms, and Clinical Research Gaps.Journal of asthma and allergy · 2026Review
- Cumulative Genetic Risk for Asthma Contributes to Disease Severity in Children with Asthma living in Urban Environments.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Evaluation of Polygenic Risk Score for Prediction of Childhood Onset and Severity of Asthma.International journal of molecular sciences · 2024Article
- Asthma-Genomic Advances Toward Risk Prediction.Clinics in chest medicine · 2024Review
- Epigenomic partitioning of a polygenic risk score for asthma reveals distinct genetically driven disease pathways.The European respiratory journal · 2024Article
- The Value Proposition of Coordinated Population Cohorts Across Africa.Annual review of biomedical data science · 2024Review
- Genetics of chronic respiratory disease.Nature reviews. Genetics · 2024Review
- Revealing polygenic pleiotropy using genetic risk scores for asthma.HGG advances · 2023Article
- A Polygenic Risk Score for Idiopathic Pulmonary Fibrosis and Interstitial Lung Abnormalities.American journal of respiratory and critical care medicine · 2023Article
- The Dunedin study after half a century: reflections on the past, and course for the future.Journal of the Royal Society of New Zealand · 2023Article
- Multi-ancestry meta-analysis of asthma identifies novel associations and highlights the value of increased power and diversity.Cell genomics · 2022Article
- Multiancestral polygenic risk score for pediatric asthma.The Journal of allergy and clinical immunology · 2022Article
- The role of epigenetics in multi-generational transmission of asthma: An NIAID workshop report-based narrative review.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2022Review
- Development and validation of an RNA-seq-based transcriptomic risk score for asthma.Scientific reports · 2022Article
- Holy Grail: the journey towards disease modification in asthma.European respiratory review : an official journal of the European Respiratory Society · 2022Review
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundGenome-wide association studies (GWAS) have discovered genetic variants that predispose individuals to asthma. To integrate these new discoveries with emerging models of asthma pathobiology, we aimed to test how genetic discoveries relate to developmental and biological characteristics of asthma.
methodsIn this prospective longitudinal study, we investigated a multilocus profile of genetic risk derived from published GWAS of asthma case status. We then tested associations between this genetic risk score and developmental and biological characteristics of asthma in participants enrolled in a population-based long-running birth cohort, the Dunedin Multidisciplinary Health and Development Study (n=1037). We used data on asthma onset, asthma persistence, atopy, airway hyper-responsiveness, incompletely reversible airflow obstruction, and asthma-related school and work absenteeism and hospital admissions obtained during nine prospective assessments spanning the ages of 9 to 38 years. Analyses included cohort members of European descent from whom genetic data had been obtained.
findingsOf the 880 cohort members included in our analysis, those at higher genetic risk developed asthma earlier in life than did those with lower genetic risk (hazard ratio [HR] 1·12, 95% CI 1·01-1·26). Of cohort members with childhood-onset asthma, those with higher genetic risk were more likely to develop life-course-persistent asthma than were those with a lower genetic risk (relative risk [RR] 1·36, 95% CI 1·14-1·63). Participants with asthma at higher genetic risk more often had atopy (RR 1·07, 1·01-1·14), airway hyper-responsiveness (RR 1·16, 1·03-1·32), and incompletely reversible airflow obstruction (RR 1·28, 1·04-1·57) than did those with a lower genetic risk. They were also more likely to miss school or work (incident rate ratio 1·38, 1·02-1·86) and be admitted to hospital (HR 1·38, 1·07-1·79) because of asthma. Genotypic information about asthma risk was independent of and additive to information derived from cohort members' family histories of asthma.
interpretationOur findings confirm that GWAS discoveries for asthma are associated with a childhood-onset phenotype. Genetic risk assessments might be able to predict which childhood-onset asthma cases remit and which become life-course-persistent, who might develop impaired lung function, and the burden of asthma in terms of missed school and work and hospital admissions, although these predictions are not sufficiently sensitive or specific to support immediate clinical translation.
fundingUS National Institute on Aging and UK Medical Research Council.
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