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

Understanding Society Scientific Group, Nick Shrine, Anna L. Guyatt, A. Mesut Erzurumluoglu, Victoria E. Jackson, Brian D. Hobbs, Carl A. 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, Stefan Weiss, Katherine A. Kentistou, James P. CookBenjamin 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, Joshua D. Hoffman, John E. Hokanson, Blair H. Smith, Martin D. Tobin, Louise V. Wain

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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.

Original languageEnglish
Pages (from-to)481-493
Number of pages13
JournalNature Genetics
Volume51
Issue number3
Early online date25 Feb 2019
DOIs
Publication statusPublished - Mar 2019

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Understanding Society Scientific Group, Shrine, N., Guyatt, A. L., Erzurumluoglu, A. M., Jackson, V. E., Hobbs, B. D., Melbourne, C. A., Batini, C., Fawcett, K. A., Song, K., Sakornsakolpat, P., Li, X., Boxall, R., Reeve, N. F., Obeidat, M., Zhao, J. H., Wielscher, M., Weiss, S., Kentistou, K. A., ... Wain, L. V. (2019). New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. Nature Genetics, 51(3), 481-493. https://doi.org/10.1038/s41588-018-0321-7