Genome-wide association study to identify genetic determinants of severe asthma

Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify common genetic variants affecting susceptibility to...

Full description

Bibliographic Details
Main Authors:	Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, Hall, Ian P.
Format:	Article
Published:	BMJ Publishing Group 2012
Online Access:	https://eprints.nottingham.ac.uk/2689/

_version_	1848790850403827712
author	Wan, Y.I. Shrine, N.R.G. Soler Artigas, M. Wain, L.V. Blakey, J.D. Moffatt, M.F. Bush, A. Chung, K. F. Cookson, W.O.C.M. Strachan, D.P. Heaney, L. Al-Momani, B.A.H. Mansur, A.H. Manney, S. Thomson, N.C. Chaudhuri, R. Brightling, C.E. Bafadhel, M. Singapuri, A. Niven, R. Simpson, A. Holloway, J.W. Howarth, P.H. Hui, J. Musk, A.W. James, A.L. Brown, M.A. Baltic, S. Ferreira, M.A.R. Thompson, P.J. Tobin, M.D. Sayers, Ian Hall, Ian P.
author_facet	Wan, Y.I. Shrine, N.R.G. Soler Artigas, M. Wain, L.V. Blakey, J.D. Moffatt, M.F. Bush, A. Chung, K. F. Cookson, W.O.C.M. Strachan, D.P. Heaney, L. Al-Momani, B.A.H. Mansur, A.H. Manney, S. Thomson, N.C. Chaudhuri, R. Brightling, C.E. Bafadhel, M. Singapuri, A. Niven, R. Simpson, A. Holloway, J.W. Howarth, P.H. Hui, J. Musk, A.W. James, A.L. Brown, M.A. Baltic, S. Ferreira, M.A.R. Thompson, P.J. Tobin, M.D. Sayers, Ian Hall, Ian P.
author_sort	Wan, Y.I.
building	Nottingham Research Data Repository
collection	Online Access
description	Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify common genetic variants affecting susceptibility to severe asthma. Methods A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10(−8) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10(−8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
first_indexed	2025-11-14T18:19:10Z
format	Article
id	nottingham-2689
institution	University of Nottingham Malaysia Campus
institution_category	Local University
last_indexed	2025-11-14T18:19:10Z
publishDate	2012
publisher	BMJ Publishing Group
recordtype	eprints
repository_type	Digital Repository
spelling	nottingham-26892020-05-04T16:33:17Z https://eprints.nottingham.ac.uk/2689/ Genome-wide association study to identify genetic determinants of severe asthma Wan, Y.I. Shrine, N.R.G. Soler Artigas, M. Wain, L.V. Blakey, J.D. Moffatt, M.F. Bush, A. Chung, K. F. Cookson, W.O.C.M. Strachan, D.P. Heaney, L. Al-Momani, B.A.H. Mansur, A.H. Manney, S. Thomson, N.C. Chaudhuri, R. Brightling, C.E. Bafadhel, M. Singapuri, A. Niven, R. Simpson, A. Holloway, J.W. Howarth, P.H. Hui, J. Musk, A.W. James, A.L. Brown, M.A. Baltic, S. Ferreira, M.A.R. Thompson, P.J. Tobin, M.D. Sayers, Ian Hall, Ian P. Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. Objective To identify common genetic variants affecting susceptibility to severe asthma. Methods A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. Results An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10(−8) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10(−8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. Conclusions The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study. BMJ Publishing Group 2012-05-05 Article PeerReviewed Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian and Hall, Ian P. (2012) Genome-wide association study to identify genetic determinants of severe asthma. Thorax, 67 (9). pp. 762-768. ISSN 0040-6376 http://thorax.bmj.com/content/67/9/762.short doi:10.1136/thoraxjnl-2011-201262 doi:10.1136/thoraxjnl-2011-201262
spellingShingle	Wan, Y.I. Shrine, N.R.G. Soler Artigas, M. Wain, L.V. Blakey, J.D. Moffatt, M.F. Bush, A. Chung, K. F. Cookson, W.O.C.M. Strachan, D.P. Heaney, L. Al-Momani, B.A.H. Mansur, A.H. Manney, S. Thomson, N.C. Chaudhuri, R. Brightling, C.E. Bafadhel, M. Singapuri, A. Niven, R. Simpson, A. Holloway, J.W. Howarth, P.H. Hui, J. Musk, A.W. James, A.L. Brown, M.A. Baltic, S. Ferreira, M.A.R. Thompson, P.J. Tobin, M.D. Sayers, Ian Hall, Ian P. Genome-wide association study to identify genetic determinants of severe asthma
title	Genome-wide association study to identify genetic determinants of severe asthma
title_full	Genome-wide association study to identify genetic determinants of severe asthma
title_fullStr	Genome-wide association study to identify genetic determinants of severe asthma
title_full_unstemmed	Genome-wide association study to identify genetic determinants of severe asthma
title_short	Genome-wide association study to identify genetic determinants of severe asthma
title_sort	genome-wide association study to identify genetic determinants of severe asthma
url	https://eprints.nottingham.ac.uk/2689/ https://eprints.nottingham.ac.uk/2689/ https://eprints.nottingham.ac.uk/2689/

Genome-wide association study to identify genetic determinants of severe asthma

Similar Items