@article{Wang2017, abstract = {The stage 1 (UK BiLEVE) genome-wide association results for FEV1, FVC and FEV1/FVC are available from UK Biobank at http://www.ukbiobank.ac.uk/. The sources of all other data utilised in this study can be found in the Online Methods and Supplementary Note. 6 Months embargo from publication. ; 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. ; This work was funded by a Medical Research Council (MRC) strategic award to M.D. Tobin, I.P. Hall, D. Strachan and L.V. Wain (MC_PC_12010). This research has been conducted using the UK Biobank Resource under Application Number 648. This article presents independent research funded partially by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This research used the ALICE and SPECTRE High Performance Computing Facilities at the University of Leicester. Additional acknowledgements and funding can be found in the Supplementary Information. ; Peer-reviewed ; Post-print}, author = {Wang, Ca A. and Wan, Es S. and Wareham, Nj J. and Zhao, Jh H. and Wilson, Jf F. and Wain, Louise V. and Walters, Rg G. and Soler Artigas, María and Mesut Erzurumluoglu, A. and Sly, Pd D. and Sparrow, Dw W. and Artigas, María Soler and Zeggini, Eleftheria and Shrine, Nick R. G. and Sin, Don D. and Henrys, Amanda P. and Thorleifsson, Gudmar and Stefansson, Kari and Vaucher, Julien and Silverman, Ek K. and Hall, Robert J. and Strachan, Dp P. and Tobin, Martin D. and Portelli, Michael A . and Erzurumluoglu, Am Mesut and Noyvert, Boris and Lv, Wain and Wielscher, Matthias and Henry, Ap P. and Bossini-Castillo, Lara and Hall, Rj J. and Billington, Ck K. and Deary, Ij J. and John, Catherine and Obeidat, Ma'en and Harris, Se E. and Kerr, Sm M. and Blake, Tineka and Stubbe, Beate and Ms, Artigas and Raitakari, Ot and Evans, Dm M. and Campbell, Archie and Pennell, Ce E. and Kähönen, Mika and Am, Erzurumluoglu and Jamess, Alan L. and Jarvelin, Marjo-Riitta and Hobbs, Bd D. and Litonjua, Aa A. and Jackson, Victoria E. and Lehtimäki, Terho and Surakka, Ida and Hui, Jennie and Rimington, Tl L. and Allen, Richard J. and Vitart, Veronique and Henderson, Aj John and van den Berge, Maarten and Fenech, Ag G. and Marten, Jonathan and Bakke, Ps S. and Rudan, Igor and Busch, Robert and Beaty, Th H. and Enroth, Stefan and Hansel, Nn N. and Mathias, Ra A. and Gulsvik, Amund and Trynka, Gosia and Rawal, Rajesh and Gyllensten, Ulf and Prins, Bp P. and Schulz, Holger and Group, Understanding Society Scientific and Polasek, Ozren and Crapo, James D. and Imboden, Medea and Barnes, Kc C. and Karrasch, Stefan and Porteous, Dj J. and Gieger, Christian and Hayward, Caroline and Ruczinski, Ingo and Bossé, Yohan and James, Al L. and Paré, Pd D. and Ap, Henry and Joubert, Philippe and Nickle, Dc C. and Joshi, Pk K. and Dewey, Fe E. and Hao, Ke and Bruse, Se E. and Gottesman, Omri and Ma, Portelli and Carey, Dj J. and Collaboration, Geisinger-Regeneron DiscovEHR and Kirchner, Hl Lester and Probst-Hensch, Nm M. and Jonsson, Stefan and Brandsma, Corry-Anke and Jonsdottir, Ingileif and Kahonen, Mika and Gislason, Thorarinn and Rj, Hall and Schurmann, Claudia and Nadkarni, Girish and Bottinger, Ep P. and Loos, Rjf J. F. and Chen, Zhengming and Millwood, Iy Y. and Kurmi, Op P. and Li, Liming and Ck, Billington and Hansell, Al L. and Brightling, Chris and Cho, Mh H. and Sayers, Ian and Grp, Understanding Soc Sci and Morris, Ap P. and Hall, Ip P. and DiscovEHR, Geisinger-Regeneron and Md, Tobin}, doi = {10.1038/ng.3787}, journal = {Nature Genetics}, month = {jan}, pages = {416-425}, title = {Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets}, url = {http://www.nature.com/articles/ng.3787.pdf}, volume = {49}, year = {2017} }