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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

Wain, Louise V. and Shrine, Nick and Artigas, María Soler and Erzurumluoglu, A. Mesut and Noyvert, Boris and Bossini-Castillo, Lara and Obeidat, Ma'en and Henry, Amanda P. and Portelli, Michael A. and Hall, Robert J. and Billington, Charlotte K. and Rimington, Tracy L. and Fenech, Anthony G. and John, Catherine and Blake, Tineka and Jackson, Victoria E. and Allen, Richard J. and Prins, Bram P. and Understanding Society Scientific Group, and Campbell, Archie and Porteous, David J. and Jarvelin, Marjo-Riitta and Wielscher, Matthias and James, Alan L. and Hui, Jennie and Wareham, Nicholas J. and Zhao, Jing Hua and Wilson, James F. and Joshi, Peter K. and Stubbe, Beate and Rawal, Rajesh and Schulz, Holger and Imboden, Medea and Probst-Hensch, Nicole M. and Karrasch, Stefan and Gieger, Christian and Deary, Ian J. and Harris, Sarah E. and Marten, Jonathan and Rudan, Igor and Enroth, Stefan and Gyllensten, Ulf and Kerr, Shona M. and Polasek, Ozren and Kähönen, Mika and Surakka, Ida and Vitart, Veronique and Hayward, Caroline and Lehtimäki, Terho and Raitakari, Olli T. and Evans, David M. and Henderson, A. John and Pennell, Craig E. and Wang, Carol A. and Sly, Peter D. and Wan, Emily S. and Busch, Robert and Hobbs, Brian D. and Litonjua, Augusto A. and Sparrow, David W. and Gulsvik, Amund and Bakke, Per S. and Crapo, James D. and Beaty, Terri H. and Hansel, Nadia N. and Mathias, Rasika A. and Ruczinski, Ingo and Barnes, Kathleen C. and Bossé, Yohan and Joubert, Philippe and van den Berge, Maarten and Brandsma, Corry-Anke and Paré, Peter D. and Sin, Don D. and Nickle, David C. and Hao, Ke and Gottesman, Omri and Dewey, Frederick E. and Bruse, Shannon E. and Carey, David J. and Kirchner, H. Lester and Jonsson, Stefan and Thorleifsson, Gudmar and Jonsdottir, Ingileif and Gislason, Thorarinn and Stefansson, Kari and Schurmann, Claudia and Nadkarni, Girish and Bottinger, Erwin P. and Loos, Ruth J. F. and Walters, Robin G. and Chen, Zhengming and Millwood, Iona Y. and Vaucher, Julien and Kurmi, Om P. and Li, Liming and Hansell, Anna L. and Brightling, Chris and Zeggini, Eleftheria and Cho, Michael H. and Silverman, Edwin K. and Sayers, Ian and Trynka, Gosia and Morris, Andrew P. and Strachan, David P. and Hall, Ian P. and Tobin, Martin D.. (2017) Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets. Nature genetics, 49 (3). pp. 416-425.

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Official URL: http://edoc.unibas.ch/55076/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
UniBasel Contributors:Imboden, Medea and Probst Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publ
ISSN:1061-4036
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:29 May 2017 13:44
Deposited On:29 May 2017 13:44

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