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

By 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 F Reeve, Ma’en Obeidat, Jing Hua Zhao, Matthias Wielscher, Understanding Society Scientific Group, 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, Veronique Vitart, Terho Lehtimäki, Richard J Allen, Per S 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 L Hansell, Ke Hao, Josh D Hoffman, John Hokanson, Georg Homuth, Peter K. Joshi, Philippe Joubert, Claudia Langenberg, Xuan Li, Liming Li, Kuang Lin, Lars Lind, Nick Locantore, Jian’an Luan, Anubha Mahajan, Joseph C. Maranville, Alison Murray, David C Nickle, Richard Packer, Margaret M Parker, Megan L Paynton, David 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 RHJ Timmers, Maarten Van den Berge, John C Whittaker, Prescott Woodruff, Laura M Yerges Armstrong, Olga G. Troyanskaya, Olli T. Raitakari, Mika Kähönen, Ozren Polasek, Ulf Gyllensten, Igor Rudan, Ian J Deary, Nicole M Probst-Hensch, Holger Schulz, Alan L James, James F Wilson, Beate Stubbe, Eleftheria Zeggini, Marjo-Riitta Jarvelin, Nicholas J. Wareham, Edwin K Silverman, Caroline Hayward, Andrew P Morris, Adam S. Butterworth, Robert A Scott, Robin G. Walters, Deborah A Meyers, Michael H Cho, David P Strachan, Ian P Hall, Martin D Tobin, Louise V Wain

Posted 12 Jun 2018
bioRxiv DOI: 10.1101/343293 (published DOI: 10.1038/s41588-018-0321-7)

Reduced lung function predicts mortality and is key to the diagnosis of COPD. In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, one-half of which are new. In combination these variants strongly predict COPD in deeply-phenotyped patient populations. Furthermore, the combined effect of these variants showed generalisability 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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