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

2019; Nature Portfolio; Volume: 51; Issue: 3 Linguagem: Inglês

10.1038/s41588-018-0321-7

1546-1718

Nick Shrine, Anna L. Guyatt, A. Mesut Erzurumluoglu, Victoria E. Jackson, Brian D. Hobbs, Carl Melbourne, Chiara Batini, Katherine A. Fawcett, Kijoung Song, Phuwanat Sakornsakolpat, Xingnan Li, Ruth Boxall, Nicola Reeve, Ma’en Obeidat, Jing Hua Zhao, Matthias Wielscher, Stefan Weiß, Katherine A. Kentistou, James P. Cook, Benjamin B. Sun, Jian Zhou, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah E. Harris, Jonathan Marten, Stefan Enroth, Shona M. Kerr, Ida Surakka, Véronique Vitart, Terho Lehtimäki, Richard J. Allen, Per Bakke, Terri H. Beaty, Eugene R. Bleecker, Yohan Bossé, Corry‐Anke Brandsma, Zhengming Chen, James D. Crapo, John Danesh, Dawn L. DeMeo, Frank Dudbridge, Ralf Ewert, Christian Gieger, Amund Gulsvik, Anna Hansell, Ke Hao, Joshua Hoffman, John E. Hokanson, Georg Homuth, Peter K. Joshi, Philippe Joubert, Claudia Langenberg, Xuan Li, Liming Li, Kuang Lin, Lars Lind, Nicholas Locantore, Jian’an Luan, Anubha Mahajan, Joseph Maranville, Alison D. Murray, David C. Nickle, Richard Packer, Margaret M. Parker, Megan L. Paynton, David J. Porteous, Dmitry Prokopenko, Dandi Qiao, Rajesh Rawal, Heiko Runz, Ian Sayers, Don D. Sin, Blair H. Smith, María Soler Artigas, David Sparrow, Ruth Tal‐Singer, Paul R. H. J. Timmers, Maarten van den Berge, John C. Whittaker, Prescott G. Woodruff, Laura M. Yerges-Armstrong, Olga G. Troyanskaya, Olli Raitakari, Mika Kähönen, Ozren Polašek, Ulf Gyllensten, Igor Rudan, Ian J. Deary, Nicole Probst‐Hensch, Holger Schulz, Anthony James, James F. Wilson, Beate Stubbe, Eleftheria Zeggini, Marjo‐Riitta Järvelin, Nicholas J. Wareham, Edwin K. Silverman, Caroline Hayward, Andrew P. Morris, Adam S. Butterworth, Robert A. Scott, Robin Walters, Deborah A. Meyers, Michael H. Cho, David P. Strachan, Ian P. Hall, Martin D. Tobin, Louise V. Wain,

Pediatric health and respiratory diseases

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 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.