SynthesisThe Lancet. Respiratory medicine2023
Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study.
Synthesis in The Lancet. Respiratory medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Exploiting meta-analysis of genome-wide interaction with serum 25-hydroxyvitamin D to identify novel genetic loci associated with pulmonary function.The American journal of clinical nutrition · 2024Pooled it
- Proteome-wide Mendelian randomisation of lung function to identify potential therapeutic targets for respiratory disease.ERJ open research · 2026Article
- Next-Generation Sequencing in Pulmonary Fibrosis: Translational Promise and Current Clinical Limitations.Current issues in molecular biology · 2026Review
- Article
- Rosmarinic acid alleviates bleomycin-induced pulmonary fibrosis in mice by activating the Rap1 pathway.Scientific reports · 2026Article
- Article
- Prospective study of fibrosis in the lung endpoints (PROFILE): characteristics of an incident cohort of patients with idiopathic pulmonary fibrosis.BMJ open respiratory research · 2026Observational
- S100A8Frontiers in immunology · 2026Article
- Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine.Frontiers in pharmacology · 2026Review
- Idiopathic Pulmonary Fibrosis: A Comprehensive Review of Risk Factors, Genetics, Diagnosis, and Therapeutic Approaches.Biomedicines · 2026Review
- Association Between Single Nucleotide Polymorphisms and Disease Susceptibility, Survival, and Acute Exacerbation in Idiopathic Pulmonary Fibrosis.Respirology (Carlton, Vic.) · 2026Observational
- Prognostic biomarkers for idiopathic pulmonary fibrosis: findings from ISABELA clinical trials.ERJ open research · 2026Article
- The role of theERJ open research · 2025Article
- Moving past multidisciplinary discussions and Gender-Age-Physiology model: precision medicine through biological phenotyping in interstitial lung disease.Current opinion in pulmonary medicine · 2025Review
- Sex-specific genetic effects on susceptibility to idiopathic pulmonary fibrosis.ERJ open research · 2025Article
- PKN2 Inhibits VEGFA and bFGF-Mediated Angiogenesis by Targeting HIF-1α in Colon Cancer.The Kaohsiung journal of medical sciences · 2025Article
- Rare variants and survival of patients with idiopathic pulmonary fibrosis: analysis of a multicentre, observational cohort study with independent validation.The Lancet. Respiratory medicine · 2025Observational
- Review
- An Overview of the Role of Genetic factors in Idiopathic Pulmonary Fibrosis: Insights from Epidemiology to Prognosis.International journal of medical sciences · 2025Review
- Differences Between Patients with Probable UIP and Definite UIP on HRCT in Idiopathic Pulmonary Fibrosis: A Real-World Cohort Study.Journal of clinical medicine · 2024Article
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Authors and funding
32 authors at 20 institutions in 3 countries.
Funding
Abstract
backgroundIdiopathic pulmonary fibrosis (IPF) is an incurable lung disease characterised by progressive scarring leading to alveolar stiffness, reduced lung capacity, and impeded gas transfer. We aimed to identify genetic variants associated with declining lung capacity or declining gas transfer after diagnosis of IPF.
methodsWe did a genome-wide meta-analysis of longitudinal measures of forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) in individuals diagnosed with IPF. Individuals were recruited to three studies between June, 1996, and August, 2017, from across centres in the US, UK, and Spain. Suggestively significant variants were investigated further in an additional independent study (CleanUP-IPF). All four studies diagnosed cases following American Thoracic Society/European Respiratory Society guidelines. Variants were defined as significantly associated if they had a meta-analysis p<5 × 10
findings1329 individuals with a total of 5216 measures were included in the FVC analysis. 975 individuals with a total of 3361 measures were included in the DLCO analysis. For the discovery genome-wide analyses, 7 611 174 genetic variants were included in the FVC analysis and 7 536 843 in the DLCO analysis. One variant (rs115982800) located in an antisense RNA gene for protein kinase N2 (PKN2) showed a genome-wide significant association with FVC decline (-140 mL/year per risk allele [95% CI -180 to -100]; p=9·14 × 10
interpretationOur analysis identifies a genetic variant associated with disease progression, which might highlight a new biological mechanism for IPF. We found that PKN2, a Rho and Rac effector protein, is the most likely gene of interest from this analysis. PKN2 inhibitors are currently in development and signify a potential novel therapeutic approach for IPF.
fundingAction for Pulmonary Fibrosis, Medical Research Council, Wellcome Trust, and National Institutes of Health National Heart, Lung, and Blood Institute.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.