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Association study of human leukocyte antigen (HLA) 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. (in press). Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis. ERJ Open Research, 00553-2023. https://doi.org/10.1183/23120541.00553-2023

IntroductionIdiopathic 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 assoc... Read More about Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis.

Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity (2023)
Journal Article
Portelli, M. A., Bhaker, S., Pang, V., Bates, D. O., Johnson, S. R., Mazar, A. P., …Sayers, I. (2023). Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity. Clinical and Translational Allergy, 13(10), Article e12293. https://doi.org/10.1002/clt2.12293

AbstractBackgroundExpression of the urokinase plasminogen activator receptor (uPAR) is elevated in the airway epithelium in asthma; however, the contribution of uPAR to asthma pathogenesis and scope for therapeutic targeting remains unknown.Objective... Read More about Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity.

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

Nepalese indoor cookstove smoke extracts alter human airway epithelial gene expression, DNA methylation and hydroxymethylation (2023)
Journal Article
Rajasekar, P., Hall, R. J., Binaya, K., Mahapatra, P. S., Puppala, S. P., Thakker, D., …Clifford, R. L. (2023). Nepalese indoor cookstove smoke extracts alter human airway epithelial gene expression, DNA methylation and hydroxymethylation. Environmental Pollution, 337, Article 122561. https://doi.org/10.1016/j.envpol.2023.122561

Household air pollution caused by inefficient cooking practices causes 4 million deaths a year worldwide. In Nepal, 86% of the rural population use solid fuels for cooking. Over 25% of premature deaths associated with air pollution are respiratory in... Read More about Nepalese indoor cookstove smoke extracts alter human airway epithelial gene expression, DNA methylation and hydroxymethylation.

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.

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.

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.

Genetics of Asthma: Insights From Genome Wide Association Studies (2021)
Book Chapter
Cooper, R. M., Bingham, K., Portelli, M. A., & Sayers, I. (2022). Genetics of Asthma: Insights From Genome Wide Association Studies. In Encyclopedia of Respiratory Medicine (308-325). (Second Edition). Elsevier. https://doi.org/10.1016/B978-0-08-102723-3.00155-4

Asthma is a heterogeneous respiratory disease that can be influenced by genetic and environmental factors leading to disease susceptibility and progression. Genome-wide association studies (GWAS) of asthma have yielded replicated findings and identif... Read More about Genetics of Asthma: Insights From Genome Wide Association Studies.

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.

Phenotypic and functional translation of IL1RL1 locus polymorphisms in lung tissue and asthmatic airway epithelium (2020)
Journal Article
Portelli, M. A., Dijk, F. N., Ketelaar, M. E., Shrine, N., Hankinson, J., Bhaker, S., …Sayers, I. (2020). Phenotypic and functional translation of IL1RL1 locus polymorphisms in lung tissue and asthmatic airway epithelium. JCI insight, 5(8), Article 132446. https://doi.org/10.1172/jci.insight.132446

The IL1RL1 (ST2) gene locus is robustly associated with asthma; however, the contribution of single nucleotide polymorphisms (SNPs) in this locus to specific asthma subtypes and the functional mechanisms underlying these associations remain to be def... Read More about Phenotypic and functional translation of IL1RL1 locus polymorphisms in lung tissue and asthmatic airway epithelium.

Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis (2019)
Journal Article
Allen, R. J., Guillen-Guio, B., Oldham, J. M., Ma, S., Dressen, A., Paynton, M. L., …Wain, L. V. (2020). Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis. American Journal of Respiratory and Critical Care Medicine, 201(5), 564-574. https://doi.org/10.1164/rccm.201905-1017oc

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of... Read More about Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis.

Exposure to lippolysaccharide (LPS) reduces contractile response of small airways from GSTCD+ mice (2019)
Journal Article
Liu, B., Henry, A. P., Azimi, S., Miller, S., Lee, F. K., Lee, J. C., …Hall, I. P. (2019). Exposure to lippolysaccharide (LPS) reduces contractile response of small airways from GSTCD+ mice. PLoS ONE, 14(9), Article e0221899. https://doi.org/10.1371/journal.pone.0221899

Introduction: Genome-Wide Association Studies suggest glutathione S transferase C terminal domain (GSTCD) may play a role in development of Chronic Obstructive Pulmonary Disease. We aimed to define the potential role of GSTCD in airway inflammation a... Read More about Exposure to lippolysaccharide (LPS) reduces contractile response of small airways from GSTCD+ mice.

Defining a role for lung function associated gene GSTCD in cell homeostasis (2019)
Journal Article
Henry, A. P., Probert, K., Stewart, C. E., Thakker, D., Bhaker, S., Azimi, S., …Sayers, I. (2019). Defining a role for lung function associated gene GSTCD in cell homeostasis. Respiratory Research, 20(1), Article 172. https://doi.org/10.1186/s12931-019-1146-3

Genome wide association (GWA) studies have reproducibly identified signals on chromosome 4q24 associated with lung function and COPD. GSTCD (Glutathione S-transferase C-terminal domain containing) represents a candidate causal gene in this locus, how... Read More about Defining a role for lung function associated gene GSTCD in cell homeostasis.

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.