New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.

Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly pre...

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Detalles Bibliográficos
Autores principales: Shrine, Nick, Guyatt, Anna L, Erzurumluoglu, A Mesut, Jackson, Victoria E, Hobbs, Brian D, Melbourne, Carl A, Batini, Chiara, Fawcett, Katherine A, Song, Kijoung, Sakornsakolpat, Phuwanat, Li, Xingnan, Boxall, Ruth, Reeve, Nicola F, Obeidat, Ma’en, Zhao, Jing Hua, Wielscher, Matthias, Weiss, Stefan, Kentistou, Katherine A, Cook, James P, Sun, Benjamin B, Zhou, Jian, Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E, Marten, Jonathan, Enroth, Stefan, Kerr, Shona M, Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Allen, Richard J, Bakke, Per S, Beaty, Terri H, Bleecker, Eugene R, Bossé, Yohan, Brandsma, Corry-Anke, Chen, Zhengming, Crapo, James D, Danesh, John, DeMeo, Dawn L, Dudbridge, Frank, Ewert, Ralf, Gieger, Christian, Gulsvik, Amund, Hansell, Anna L, Hao, Ke, Hoffman, Joshua D, Hokanson, John E, Homuth, Georg, Joshi, Peter K, Joubert, Philippe, Langenberg, Claudia, Li, Xuan, Li, Liming, Lin, Kuang, Lind, Lars, Locantore, Nicholas, Luan, Jian’an, Mahajan, Anubha, Maranville, Joseph C, Murray, Alison, Nickle, David C, Packer, Richard, Parker, Margaret M, Paynton, Megan L, Porteous, David J, Prokopenko, Dmitry, Qiao, Dandi, Rawal, Rajesh, Runz, Heiko, Sayers, Ian, Sin, Don D, Smith, Blair H, Artigas, María Soler, Sparrow, David, Tal-Singer, Ruth, Timmers, Paul RHJ, Van den Berge, Maarten, Whittaker, John C, Woodruff, Prescott G, Yerges-Armstrong, Laura M, Troyanskaya, Olga G, Raitakari, Olli T, Kähönen, Mika, Polasek, Ozren, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J, Probst-Hensch, Nicole M, Schulz, Holger, James, Alan L, Wilson, James F, Stubbe, Beate, Zeggini, Eleftheria, Jarvelin, Marjo-Riitta, Wareham, Nick, Silverman, Edwin K, Hayward, Caroline, Morris, Andrew P, Butterworth, Adam S, Scott, Robert A, Walters, Robin G, Meyers, Deborah A, Cho, Michael H, Strachan, David P, Hall, Ian P, Tobin, Martin D, Wain, Louise V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397078/
https://www.ncbi.nlm.nih.gov/pubmed/30804560
http://dx.doi.org/10.1038/s41588-018-0321-7
Descripción
Sumario:Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent patient populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

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