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

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 in...

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Detalles Bibliográficos
Autores principales: Wain, Louise V, Shrine, Nick, Soler Artigas, María, Erzurumluoglu, A Mesut, Noyvert, Boris, Bossini-Castillo, Lara, Obeidat, Ma’en, Henry, Amanda P, Portelli, Michael A, Hall, Robert J, Billington, Charlotte K, Rimington, Tracy L, Fenech, Anthony G, John, Catherine, Blake, Tineka, Jackson, Victoria E, Allen, Richard J, Prins, Bram P, Campbell, Archie, Porteous, David J, Jarvelin, Marjo-Riitta, Wielscher, Matthias, James, Alan L, Hui, Jennie, Wareham, Nicholas J, Zhao, Jing Hua, Wilson, James F, Joshi, Peter K, Stubbe, Beate, Rawal, Rajesh, Schulz, Holger, Imboden, Medea, Probst-Hensch, Nicole M, Karrasch, Stefan, Gieger, Christian, Deary, Ian J, Harris, Sarah E, Marten, Jonathan, Rudan, Igor, Enroth, Stefan, Gyllensten, Ulf, Kerr, Shona M, Polasek, Ozren, Kähönen, Mika, Surakka, Ida, Vitart, Veronique, Hayward, Caroline, Lehtimäki, Terho, Raitakari, Olli T, Evans, David M, Henderson, A John, Pennell, Craig E, Wang, Carol A, Sly, Peter D, Wan, Emily S, Busch, Robert, Hobbs, Brian D, Litonjua, Augusto A, Sparrow, David W, Gulsvik, Amund, Bakke, Per S, Crapo, James D, Beaty, Terri H, Hansel, Nadia N, Mathias, Rasika A, Ruczinski, Ingo, Barnes, Kathleen C, Bossé, Yohan, Joubert, Philippe, van den Berge, Maarten, Brandsma, Corry-Anke, Paré, Peter D, Sin, Don D, Nickle, David C, Hao, Ke, Gottesman, Omri, Dewey, Frederick E, Bruse, Shannon E, Carey, David J, Kirchner, H Lester, Jonsson, Stefan, Thorleifsson, Gudmar, Jonsdottir, Ingileif, Gislason, Thorarinn, Stefansson, Kari, Schurmann, Claudia, Nadkarni, Girish, Bottinger, Erwin P, Loos, Ruth JF, Walters, Robin G, Chen, Zhengming, Millwood, Iona Y, Vaucher, Julien, Kurmi, Om P, Li, Liming, Hansell, Anna L, Brightling, Chris, Zeggini, Eleftheria, Cho, Michael H, Silverman, Edwin K, Sayers, Ian, Trynka, Gosia, Morris, Andrew P, Strachan, David P, Hall, Ian P, Tobin, Martin D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326681/
https://www.ncbi.nlm.nih.gov/pubmed/28166213
http://dx.doi.org/10.1038/ng.3787
Descripción
Sumario: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.

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