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Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk (2023)
Journal Article
Shrine, N., Izquierdo, A. G., Chen, J., Packer, R., Hall, R. J., Guyatt, A. L., …Consortium Lead Principal Investigators. (2023). Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk. Nature Genetics, 55, 1778–1779. https://doi.org/10.1038/s41588-023-01531-7

Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection (2023)
Journal Article
Packer, R. J., Shrine, N., Hall, R., Melbourne, C. A., Thompson, R., Williams, A. T., …Wain, L. V. (2023). Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection. European Respiratory Journal, 61(6), Article 2201667. https://doi.org/10.1183/13993003.01667-2022

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its cause... Read More about Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk (2023)
Journal Article
Shrine, N., Izquierdo, A. G., Chen, J., Packer, R., Hall, R. J., Guyatt, A. L., …The Qatar Genome Program Research (QGPR) Consortium. (2023). Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk. Nature Genetics, 55(3), 410-422. https://doi.org/10.1038/s41588-023-01314-0

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020... Read More about Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis (2023)
Journal Article
Guillen-Guio, B., Paynton, M. L., Allen, R. J., Chin, D. P., Donoghue, L. J., Stockwell, A., …Hollox, E. J. (2024). Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis. ERJ Open Research, 10(1), 00553-2023. https://doi.org/10.1183/23120541.00553-2023

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior ass... Read More about Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis.

Exome-wide analysis of copy number variation shows association of the human leukocyte antigen region with asthma in UK Biobank (2022)
Journal Article
Fawcett, K. A., Demidov, G., Shrine, N., Paynton, M. L., Ossowski, S., Sayers, I., …Hollox, E. J. (2022). Exome-wide analysis of copy number variation shows association of the human leukocyte antigen region with asthma in UK Biobank. BMC Medical Genomics, 15, Article 119. https://doi.org/10.1186/s12920-022-01268-y

Background The role of copy number variants (CNVs) in susceptibility to asthma is not well understood. This is, in part, due to the difficulty of accurately measuring CNVs in large enough sample sizes to detect associations. The recent availability... Read More about Exome-wide analysis of copy number variation shows association of the human leukocyte antigen region with asthma in UK Biobank.

Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease (2022)
Journal Article
Guyatt, A., John, C., Williams, A. T., Shrine, N., Reeve, N. F., Sayers, I., …SpiroMeta consortium. (2023). Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease. Thorax, 78(5), 496-503. https://doi.org/10.1136/thoraxjnl-2021-217993

Rationale Eosinophils are associated with airway inflammation in respiratory disease. Eosinophil production and survival is controlled partly by interleukin-5: anti-interleukin-5 agents reduce asthma and response correlates with baseline eosinophil c... Read More about Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease.

Genetic Associations and Architecture of Asthma-COPD Overlap (2022)
Journal Article
John, C., Guyatt, A. L., Shrine, N., Packer, R., Olafsdottir, T. A., Liu, J., …Tobin, M. D. (2022). Genetic Associations and Architecture of Asthma-COPD Overlap. Chest, 161(5), 1155-1166. https://doi.org/10.1016/j.chest.2021.12.674

Background Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. Research Question What is the genetic architecture of asthma-CO... Read More about Genetic Associations and Architecture of Asthma-COPD Overlap.

Translational Analysis of Moderate to Severe Asthma GWAS Signals Into Candidate Causal Genes and Their Functional, Tissue-Dependent and Disease-Related Associations (2021)
Journal Article
Portelli, M. A., Rakkar, K., Hu, S., Guo, Y., Adcock, I. M., & Sayers, I. (2021). Translational Analysis of Moderate to Severe Asthma GWAS Signals Into Candidate Causal Genes and Their Functional, Tissue-Dependent and Disease-Related Associations. Frontiers in Allergy, 2, Article 738741. https://doi.org/10.3389/falgy.2021.738741

Asthma affects more than 300 million people globally and is both under diagnosed and under treated. The most recent and largest genome-wide association study investigating moderate to severe asthma to date was carried out in 2019 and identified 25 in... Read More about Translational Analysis of Moderate to Severe Asthma GWAS Signals Into Candidate Causal Genes and Their Functional, Tissue-Dependent and Disease-Related Associations.

Functional genomics of GPR126 in airway smooth muscle and bronchial epithelial cells (2021)
Journal Article
Hall, R. J., O'Loughlin, J., Billington, C. K., Thakker, D., Hall, I. P., & Sayers, I. (2021). Functional genomics of GPR126 in airway smooth muscle and bronchial epithelial cells. FASEB Journal, 35(7), Article e21300. https://doi.org/10.1096/fj.202002073R

GPR126 is an adhesion G protein-coupled receptor which lies on chromosome 6q24. Genetic variants in this region are reproducibly associated with lung function and COPD in genome wide association studies (GWAS). The aims of this study were to define t... Read More about Functional genomics of GPR126 in airway smooth muscle and bronchial epithelial cells.

Epithelial cell dysfunction, a major driver of asthma development (2020)
Journal Article
Heijink, I. H., Kuchibhotla, V. N. S., Roffel, M. P., Maes, T., Knight, D. A., Sayers, I., & Nawijn, M. C. (2020). Epithelial cell dysfunction, a major driver of asthma development. Allergy, 75(8), 1902-1917. https://doi.org/10.1111/all.14421

Airway epithelial barrier dysfunction is frequently observed in asthma and may have important implications. The physical barrier function of the airway epithelium is tightly interwoven with its immunomodulatory actions, while abnormal epithelial repa... Read More about Epithelial cell dysfunction, a major driver of asthma development.

Phenotypic and functional translation of IL33 genetics in asthma (2020)
Journal Article
Ketelaar, M. E., Portelli, M. A., Dijk, F. N., Shrine, N., Faiz, A., Vermeulen, C. J., …Nawijn, M. C. (2021). Phenotypic and functional translation of IL33 genetics in asthma. Journal of Allergy and Clinical Immunology, 147(1), 144-157. https://doi.org/10.1016/j.jaci.2020.04.051

© 2020 Background: Asthma is a complex disease with multiple phenotypes that may differ in disease pathobiology and treatment response. IL33 single nucleotide polymorphisms (SNPs) have been reproducibly associated with asthma. IL33 levels are elevate... Read More about Phenotypic and functional translation of IL33 genetics in asthma.

New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries (2019)
Journal Article
Shrine, N., Guyatt, A. L., Erzurumluoglu, A. M., Jackson, V. E., Hobbs, B. D., Melbourne, C. A., …Wain, L. V. (2019). New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. Nature Genetics, 51(3), 481-493. https://doi.org/10.1038/s41588-018-0321-7

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which ar... Read More about New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.

Genetic risk factors for the development of pulmonary disease identified by genome-wide association (2018)
Journal Article
Hall, R., Hall, I. P., & Sayers, I. (2018). Genetic risk factors for the development of pulmonary disease identified by genome-wide association. Respirology, 24(3), 204-214. https://doi.org/10.1111/resp.13436

Chronic respiratory diseases are a major cause of morbidity and mortality. Asthma and chronic obstructive pulmonary disease (COPD) combined affect over 500 million people worldwide. While environmental factors are important in disease progression, as... Read More about Genetic risk factors for the development of pulmonary disease identified by genome-wide association.

Addressing unmet needs in understanding asthma mechanisms (2017)
Journal Article
Edwards, M. R., Saglani, S., Schwarze, J., Skevaki, C., Smith, J. A., Ainsworth, B., …Wheelock, C. (2017). Addressing unmet needs in understanding asthma mechanisms. European Respiratory Journal, 49(5), Article 1602448. https://doi.org/10.1183/13993003.02448-2016

Asthma is a heterogeneous, complex disease with clinical phenotypes that incorporate persistent symptoms and acute exacerbations. It affects many millions of Europeans throughout their education and working lives and puts a heavy cost on European pro... Read More about Addressing unmet needs in understanding asthma mechanisms.

Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways (2017)
Journal Article
Kheirallah, A. K., de Moor, C. H., Faiz, A., Sayers, I., & Hall, I. P. (2017). Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways. BMC Genomics, 18(1), Article 248. https://doi.org/10.1186/s12864-017-3628-3

BACKGROUND: Genetic studies of human lung function and Chronic Obstructive Pulmonary Disease have identified a highly significant and reproducible signal on 4q24. It remains unclear which of the two candidate genes within this locus may regulate lung... Read More about Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways.

Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls (2017)
Journal Article
Artigas, M. S., Wain, L. V., Shrine, N., McKeever, T. M., Sayers, I., Hall, I. P., & Tobin, M. D. (2017). Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls. PLoS ONE, 12(1), Article e0170222. https://doi.org/10.1371/journal.pone.0170222

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS) of the lung function meas... Read More about Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls.

Genome-wide association studies in asthma (2016)
Journal Article
Portelli, M. A., & Sayers, I. (in press). Genome-wide association studies in asthma. https://doi.org/10.1002/9780470015902.a0024639

Asthma is a complex respiratory disease, with both genetic and environmental factors contributing to disease susceptibility. Genome-wide association studies (GWAS) have now identified novel risk alleles and loci associated with asthma diagnosis and m... Read More about Genome-wide association studies in asthma.

Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients (2016)
Journal Article
Portelli, M. A., Moseley, C., Stewart, C. E., Postma, D. S., Howarth, P., Warner, J., …Sayers, I. (in press). Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients. Allergy, https://doi.org/10.1111/all.13046

Rationale: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studieshave identified uPAR... Read More about Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients.

Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development (2016)
Journal Article
Miller, S., Melén, E., Merid, S. K., Hall, I. P., & Sayers, I. (in press). Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development. Respiratory Research, 17(95), https://doi.org/10.1186/s12931-016-0410-z

Background Recent meta-analyses of genome-wide association studies have identified single nucleotide polymorphisms (SNPs) within/near 54 genes associated with lung function measures. Current understanding of the contribution of these genes to human... Read More about Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development.