A genome wide association study of moderate-severe asthma in subjects from the United Kingdom

Shrine, Nick, Soler-Artigas, Maria, Portelli, Michael, Bennett, Neil D., Ntalla, Ioanna, Henry, Amanda, Billington, Charlotte K., Shaw, Dominic, Pogson, Zara E.K., Fogarty, Andrew, McKeever, Tricia, Jonker, Leon ORCID: https://orcid.org/0000-0001-5867-4663 , Singapuri, Amisha, Heaney, Liam, Mansur, Adel, Chaudhuri, Rekha, Thomson, Neil, Holloway, John, Lockett, Gabrielle, Howarth, Peter, Djukanovic, Ratko, Hankinson, Jenny, Niven, Richard, Simpson, Angela, Chung, Kian, Sterk, Peter, Blakey, John, Adcock, Ian, Tobin, Martin, Hall, Ian, Brightling, Chris E., Wain, Louise and Sayers, Ian (2017) A genome wide association study of moderate-severe asthma in subjects from the United Kingdom. European Respiratory Journal, 50 (S61). PA1815.

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Abstract

Rationale: Genome wide association studies (GWAS) in asthma have been successful in identifying disease susceptibility genes, however to date these have focused on mild disease. The genetic risk factors for moderate-severe asthma remain unclear.

Aim: To identify common genetic variants affecting susceptibility to develop moderate-severe asthma.

Methods: We identified asthma cases and controls from UK Biobank and additional cases from the Genetics of Asthma Severity & Phenotypes (GASP) cohort. A genome-wide association study was undertaken in 5,135 European ancestry individuals with moderate-severe asthma based on British Thoracic Society criteria 3 or above and 25,675 controls free from lung disease, allergic rhinitis and atopic dermatitis. After imputation (UK10K + 1000 genomes Phase 3) and standard quality control measures, the association of 33,771,858 single nucleotide polymorphisms (SNPs) were tested. A logistic model of association of asthma status with imputed genotype dose was fitted using SNPTEST adjusted for ancestry principal components.

Results: We identified 22 loci showing association (P < 5 × 10(-8)) including novel signals in or near D2HGDH, STAT6, HLA-B, CD247, GATA3, PDCD1LG2, ZNF652, RPAP3, MUC5AC and BACH2. Previously described asthma loci where replicated including signals in or near HLA-DQB1, TSLP, IL1RL1/IL18R1, CLEC16A, GATA3, IL33, SMAD3, SLC22A5/IL13, C11orf30, ZBTB10, IKZF3-ORMDL3 and IKZF4.

Conclusion: The largest genome-wide association study of moderate-severe asthma to date was carried out and multiple novel loci where identified. These findings may provide new insight into the molecular mechanisms underlying this difficult to treat population.

Item Type:	Article
Journal / Publication Title:	European Respiratory Journal
Publisher:	European Respiratory Society / Wiley
ISSN:	1399-3003
Departments:	Professional Services > Marketing & Student Recruitment
Additional Information:	Abstract presented at: 27th International Congress of the European Respiratory Society (ERS International Congress 2017), Milan, Italy, 9-13 September 2017.
Depositing User:	Anna Lupton
Date Deposited:	15 Mar 2018 11:47
Last Modified:	12 Jan 2024 18:16
URI:	https://insight.cumbria.ac.uk/id/eprint/3667

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