New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.
Authors
Melbourne, Carl A
Batini, Chiara
Song, Kijoung
Li, Xingnan
Boxall, Ruth
Reeve, Nicola F
Wielscher, Matthias
Weiss, Stefan
Cook, James P
Sun, Ben
Zhou, Jian
Karrasch, Stefan
Imboden, Medea
Harris, Sarah E
Kerr, Shona M
Surakka, Ida
Lehtimäki, Terho
Bakke, Per S
Bleecker, Eugene R
Brandsma, Corry-Anke
Chen, Zhengming
Crapo, James D
DeMeo, Dawn L
Dudbridge, Frank
Ewert, Ralf
Gieger, Christian
Gulsvik, Amund
Hansell, Anna L
Hao, Ke
Hoffman, Joshua D
Hokanson, John E
Homuth, Georg
Joubert, Philippe
Li, Xuan
Li, Liming
Lin, Kuang
Lind, Lars
Locantore, Nicholas
Maranville, Joseph C
Nickle, David C
Parker, Margaret M
Paynton, Megan L
Prokopenko, Dmitry
Qiao, Dandi
Rawal, Rajesh
Runz, Heiko
Sin, Don D
Soler Artigas, María
Whittaker, John C
Yerges-Armstrong, Laura M
Raitakari, Olli T
Polašek, Ozren
Gyllensten, Ulf
Deary, Ian J
Probst-Hensch, Nicole M
Schulz, Holger
James, Alan L
Stubbe, Beate
Jarvelin, Marjo-Riitta
Silverman, Edwin K
Scott, Robert A
Meyers, Deborah A
Hall, Ian P
Wain, Louise V
Publication Date
2019-03Journal Title
Nature genetics
ISSN
1061-4036
Publisher
Springer Nature
Volume
51
Issue
3
Pages
481-493
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Shrine, N., Guyatt, A. L., Erzurumluoglu, A. M., Jackson, V. E., Hobbs, B. D., Melbourne, C. A., Batini, C., et al. (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
Abstract
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, 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.
Keywords
Understanding Society Scientific Group, Lung, Humans, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Risk Factors, Case-Control Studies, Smoking, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study
Sponsorship
MRC (MC_UU_12015/1)
MRC (1508647)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
MRC (MC_PC_13048)
British Heart Foundation (RG/13/13/30194)
British Heart Foundation (RG/18/13/33946)
Identifiers
External DOI: https://doi.org/10.1038/s41588-018-0321-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288299
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