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Title: Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets
Authors: Wain, Louise V.
Shrine, Nick
Soler Artigas, María
Erzurumluoglu, A. Mesut
Noyvert, Boris
Bossini-Castillo, L.
Obeidat, M.
Henry, A. P.
Portelli, M. A .
Hall, R. J.
Billington, C. K.
Silverman, E. K.
Sayers, I.
Trynka, G.
Morris, A. P.
Strachan, D. P.
Hall, I. P.
Tobin, Martin D.
Rimington, T. L.
Fenech, A. G.
John, Catherine
Blake, Tineka
Jackson, Victoria E.
Allen, Richard J.
Prins, B. P.
Understanding Society Scientific Group
Campbell, A.
Porteous, D. J.
Jarvelin, M-R.
Wielscher, M.
James, A. L.
Hui, J.
Wareham, N. J
Zhao, J. H.
Wilson, J. F.
Joshi, P. K.
Stubbe, B.
Rawal, R.
Schulz, H.
Imboden, M.
Probst-Hensch, N. M.
Karrasch, S.
Gieger, C.
Deary, I. J.
Harris, S. E.
Marten, J.
Rudan, I.
Enroth, S.
Gyllensten, U.
Kerr, S. M.
Polasek, O.
Kähönen, M.
Surakka, I.
Vitart, V.
Hayward, C.
Lehtimäki, T.
Raitakari, O.
Evans, D. M.
Henderson, A. J.
Pennell, C. E.
Wang, C. A.
Sly, P. D.
Wan, E. S.
Busch, R.
Hobbs, B. D.
Litonjua, A. A.
Sparrow, D. W.
Gulsvik, A.
Bakke, P. S.
Crapo, J. D.
Beaty, T. H.
Hansel, N. N.
Mathias, R. A.
Ruczinski, I.
Barnes, K. C.
Bossé, Y.
Joubert, P.
van den Berge, M.
Brandsma, C-A.
Paré, P. D.
Sin, D. D.
Nickle, D. C.
Hao, K.
Gottesman, O.
Dewey, F. E.
Bruse, S. E.
Carey, D. J.
Kirchner, H. L.
Geisinger-Regeneron DiscovEHR Collaboration
Jonsson, S.
Thorleifsson, G.
Jonsdottir, I.
Gislason, T.
Stefansson, K.
Schurmann, C.
Nadkarni, G.
Bottinger, E. P.
Loos, R. J. F.
Walters, R. G.
Chen, Z.
Millwood, I. Y.
Vaucher, J.
Kurmi, O. P.
Li, L.
Hansell, A. L.
Brightling, Chris
Zeggini, E.
Cho, M. H.
First Published: 6-Feb-2017
Publisher: Nature Publishing Group
Citation: Nature Genetics, 2017
Abstract: Chronic Obstructive Pulmonary Disease (COPD) is characterised by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratios per standard deviation of the risk score (~6 alleles) (95% confidence interval) 1.24 (1.20-1.27), P=5.05x10^-49) and we observed a 3.7 fold difference in COPD risk between highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in development, elastic fibres and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
DOI Link: 10.1038/ng.3787
ISSN: 1061-4036
eISSN: 1546-1718
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Creative Commons “Attribution Non-Commercial No Derivatives” licence CC BY-NC-ND, further details of which can be found via the following link: Archived with reference to SHERPA/RoMEO and publisher website.
Description: The stage 1 (UK BiLEVE) genome-wide association results for FEV1, FVC and FEV1/FVC are available from UK Biobank at The sources of all other data utilised in this study can be found in the Online Methods and Supplementary
The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Health Sciences

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