New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. Author Nick Shrine, Anna Guyatt, A Mesut Erzurumluoglu, Victoria Jackson, Brian Hobbs, Carl Melbourne, Chiara Batini, Katherine Fawcett, Kijoung Song, Phuwanat Sakornsakolpat, Xingnan Li, Ruth Boxall, Nicola Reeve, Ma'en Obeidat, Jing Zhao, Matthias Wielscher, Stefan Weiss, Katherine Kentistou, James Cook, Benjamin Sun, Jian Zhou, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah Harris, Jonathan Marten, Stefan Enroth, Shona Kerr, Ida Surakka, Veronique Vitart, Terho Lehtimäki, Richard Allen, Per Bakke, Terri Beaty, Eugene Bleecker, Yohan Bossé, Corry-Anke Brandsma, Zhengming Chen, James Crapo, John Danesh, Dawn DeMeo, Frank Dudbridge, Ralf Ewert, Christian Gieger, Amund Gulsvik, Anna Hansell, Ke Hao, Joshua Hoffman, John Hokanson, Georg Homuth, Peter Joshi, Philippe Joubert, Claudia Langenberg, Xuan Li, Liming Li, Kuang Lin, Lars Lind, Nicholas Locantore, Jian'an Luan, Anubha Mahajan, Joseph Maranville, Alison Murray, David Nickle, Richard Packer, Margaret Parker, Megan Paynton, David Porteous, Dmitry Prokopenko, Dandi Qiao, Rajesh Rawal, Heiko Runz, Ian Sayers, Don Sin, Blair Smith, María Artigas, David Sparrow, Ruth Tal-Singer, Paul Timmers, Maarten Van den Berge, John Whittaker, Prescott Woodruff, Laura Yerges-Armstrong, Olga Troyanskaya, Olli Raitakari, Mika Kähönen, Ozren Polašek, Ulf Gyllensten, Igor Rudan, Ian Deary, Nicole Probst-Hensch, Holger Schulz, Alan James, James Wilson, Beate Stubbe, Eleftheria Zeggini, Marjo-Riitta Jarvelin, Nick Wareham, Edwin Silverman, Caroline Hayward, Andrew Morris, Adam Butterworth, Robert Scott, Robin Walters, Deborah Meyers, Michael Cho, David Strachan, Ian Hall, Martin Tobin, Louise Wain, Understanding Society Scientific Group Publication Year 2019 Type Journal Article Abstract 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. Keywords Humans, Female, Male, Genetic Predisposition to Disease, Middle Aged, Polymorphism, Single Nucleotide, Lung, Genome-Wide Association Study, Aged, Aged, 80 and over, Case-Control Studies, Risk Factors, Pulmonary Disease, Chronic Obstructive, Smoking Journal Nat Genet Volume 51 Issue 3 Pages 481-493 Date Published 2019 Mar ISSN Number 1546-1718 DOI 10.1038/s41588-018-0321-7 Alternate Journal Nat Genet PMCID PMC6397078 PMID 30804560 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML
