Wain, LV;
Shrine, N;
Artigas, MS;
Erzurumluoglu, AM;
Noyvert, B;
Bossini-Castillo, L;
Obeidat, M;
Henry, AP;
Portelli, MA;
Hall, RJ;
et al.
Wain, LV; Shrine, N; Artigas, MS; Erzurumluoglu, AM; Noyvert, B; Bossini-Castillo, L; Obeidat, M; Henry, AP; Portelli, MA; Hall, RJ; Billington, CK; Rimington, TL; Fenech, AG; John, C; Blake, T; Jackson, VE; Allen, RJ; Prins, BP; Understanding Society Scientific Group; Campbell, A; Porteous, DJ; Jarvelin, M-R; Wielscher, M; James, AL; Hui, J; Wareham, NJ; Zhao, JH; Wilson, JF; Joshi, PK; Stubbe, B; Rawal, R; Schulz, H; Imboden, M; Probst-Hensch, NM; Karrasch, S; Gieger, C; Deary, IJ; Harris, SE; Marten, J; Rudan, I; Enroth, S; Gyllensten, U; Kerr, SM; Polasek, O; Kähönen, M; Surakka, I; Vitart, V; Hayward, C; Lehtimäki, T; Raitakari, OT; Evans, DM; Henderson, AJ; Pennell, CE; Wang, CA; Sly, PD; Wan, ES; Busch, R; Hobbs, BD; Litonjua, AA; Sparrow, DW; Gulsvik, A; Bakke, PS; Crapo, JD; Beaty, TH; Hansel, NN; Mathias, RA; Ruczinski, I; Barnes, KC; Bossé, Y; Joubert, P; van den Berge, M; Brandsma, C-A; Paré, PD; Sin, DD; Nickle, DC; Hao, K; Gottesman, O; Dewey, FE; Bruse, SE; Carey, DJ; Kirchner, HL; Geisinger-Regeneron DiscovEHR Collaboration; Jonsson, S; Thorleifsson, G; Jonsdottir, I; Gislason, T; Stefansson, K; Schurmann, C; Nadkarni, G; Bottinger, EP; Loos, RJF; Walters, RG; Chen, Z; Millwood, IY; Vaucher, J; Kurmi, OP; Li, L; Hansell, AL; Brightling, C; Zeggini, E; Cho, MH; Silverman, EK; Sayers, I; Trynka, G; Morris, AP; Strachan, DP; Hall, IP; Tobin, MD
(2017)
Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
Nat Genet, 49 (3).
pp. 416-425.
ISSN 1546-1718
https://doi.org/10.1038/ng.3787
SGUL Authors: Strachan, David Peter
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Abstract
Chronic obstructive pulmonary disease (COPD) is characterized 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 ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers 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.
Item Type: | Article | ||||||||
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Additional Information: | © 2017 Nature America, Inc., part of Springer Nature. All rights reserved. | ||||||||
Keywords: | Developmental Biology, 11 Medical And Health Sciences, 06 Biological Sciences | ||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Population Health Research Institute (INPH) | ||||||||
Journal or Publication Title: | Nat Genet | ||||||||
ISSN: | 1546-1718 | ||||||||
Language: | eng | ||||||||
Dates: |
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Publisher License: | Publisher's own licence | ||||||||
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PubMed ID: | 28166213 | ||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/108532 | ||||||||
Publisher's version: | https://doi.org/10.1038/ng.3787 |
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