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

Nick R G Shrine, Anna 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, Nicole F. Reeve, Ma'en Obeidat, Jing Hua Zhao, Matthias Wielscher, Understanding Society Scientific Group, Stefan Weiss, Katherine Kentistou, James P. CookBenjamin B. Sun, Jian Zhou, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah Harris, Jonathan Marten, Stefan Enroth, Shona 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, Joshua D Hoffman, John E Hokanson, Georg Homuth, Peter 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, Maria Soler Artigas, David Sparrow, Ruth Tal-Singer, Paul RHJ Timmers, Maarten van den Berge, Prescott G Woodruff, Laura M Yerges-Armstrong, Olga G. Troyanskaya, Olli . Raitakar, Mika Kähönen, Ozren Polasek, Igor Rudan, Ian Deary, Nicole M Probst-Hensch, Holger Schulz, Alan L. James, James F Wilson, Beate Stubbe, Eleftheria Zeggini, Marjo-Riitta Jarvelin, Nick 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

Research output: Contribution to journalArticlepeer-review

Abstract

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, 139 of which are new. In combination, these variants strongly predict COPD in independent 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.
Original languageEnglish
Pages (from-to)481–493
JournalNature Genetics
Volume51
Early online date25 Feb 2019
DOIs
Publication statusPublished - 2019

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