TY - JOUR
T1 - A genome wide association study of moderate-severe asthma in subjects from the United Kingdom
AU - Shrine, Nick
AU - Soler-Artigas, Maria
AU - Portelli, Michael
AU - Bennett, Neil D.
AU - Ntalla, Ioanna
AU - Henry, Amanda
AU - Billington, Charlotte K.
AU - Shaw, Dominic
AU - Pogson, Zara E.K.
AU - Fogarty, Andrew
AU - McKeever, Tricia
AU - Jonker, Leon
AU - Singapuri, Amisha
AU - Heaney, Liam
AU - Mansur, Adel
AU - Chaudhuri, Rekha
AU - Thomson, Neil
AU - Holloway, John
AU - Lockett, Gabrielle
AU - Howarth, Peter
AU - Djukanovic, Ratko
AU - Hankinson, Jenny
AU - Niven, Richard
AU - Simpson, Angela
AU - Chung, Kian
AU - Sterk, Peter
AU - Blakey, John
AU - Adcock, Ian
AU - Tobin, Martin
AU - Hall, Ian
AU - Brightling, Chris E.
AU - Wain, Louise
AU - Sayers, Ian
N1 - Abstract presented at: 27th International Congress of the European Respiratory Society (ERS International Congress 2017), Milan, Italy, 9-13 September 2017.
PY - 2017/12/6
Y1 - 2017/12/6
N2 - 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.
AB - 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.
KW - asthma
KW - genetics
U2 - 10.1183/1393003.congress-2017.PA1815
DO - 10.1183/1393003.congress-2017.PA1815
M3 - Journal Article
SN - 0903-1936
VL - 50
SP - PA1815
JO - European Respiratory Journal
JF - European Respiratory Journal
ER -