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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.
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 pre...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397078/ https://www.ncbi.nlm.nih.gov/pubmed/30804560 http://dx.doi.org/10.1038/s41588-018-0321-7 |
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author | Shrine, Nick Guyatt, Anna L Erzurumluoglu, A Mesut Jackson, Victoria E Hobbs, Brian D Melbourne, Carl A Batini, Chiara Fawcett, Katherine A Song, Kijoung Sakornsakolpat, Phuwanat Li, Xingnan Boxall, Ruth Reeve, Nicola F Obeidat, Ma’en Zhao, Jing Hua Wielscher, Matthias Weiss, Stefan Kentistou, Katherine A Cook, James P Sun, Benjamin B Zhou, Jian Hui, Jennie Karrasch, Stefan Imboden, Medea Harris, Sarah E Marten, Jonathan Enroth, Stefan Kerr, Shona M Surakka, Ida Vitart, Veronique Lehtimäki, Terho Allen, Richard J Bakke, Per S Beaty, Terri H Bleecker, Eugene R Bossé, Yohan Brandsma, Corry-Anke Chen, Zhengming Crapo, James D Danesh, John DeMeo, Dawn L Dudbridge, Frank Ewert, Ralf Gieger, Christian Gulsvik, Amund Hansell, Anna L Hao, Ke Hoffman, Joshua D Hokanson, John E Homuth, Georg Joshi, Peter K Joubert, Philippe Langenberg, Claudia Li, Xuan Li, Liming Lin, Kuang Lind, Lars Locantore, Nicholas Luan, Jian’an Mahajan, Anubha Maranville, Joseph C Murray, Alison Nickle, David C Packer, Richard Parker, Margaret M Paynton, Megan L Porteous, David J Prokopenko, Dmitry Qiao, Dandi Rawal, Rajesh Runz, Heiko Sayers, Ian Sin, Don D Smith, Blair H Artigas, María Soler Sparrow, David Tal-Singer, Ruth Timmers, Paul RHJ Van den Berge, Maarten Whittaker, John C Woodruff, Prescott G Yerges-Armstrong, Laura M Troyanskaya, Olga G Raitakari, Olli T Kähönen, Mika Polasek, Ozren Gyllensten, Ulf Rudan, Igor Deary, Ian J Probst-Hensch, Nicole M Schulz, Holger James, Alan L Wilson, James F Stubbe, Beate Zeggini, Eleftheria Jarvelin, Marjo-Riitta Wareham, Nick Silverman, Edwin K Hayward, Caroline Morris, Andrew P Butterworth, Adam S Scott, Robert A Walters, Robin G Meyers, Deborah A Cho, Michael H Strachan, David P Hall, Ian P Tobin, Martin D Wain, Louise V |
author_facet | Shrine, Nick Guyatt, Anna L Erzurumluoglu, A Mesut Jackson, Victoria E Hobbs, Brian D Melbourne, Carl A Batini, Chiara Fawcett, Katherine A Song, Kijoung Sakornsakolpat, Phuwanat Li, Xingnan Boxall, Ruth Reeve, Nicola F Obeidat, Ma’en Zhao, Jing Hua Wielscher, Matthias Weiss, Stefan Kentistou, Katherine A Cook, James P Sun, Benjamin B Zhou, Jian Hui, Jennie Karrasch, Stefan Imboden, Medea Harris, Sarah E Marten, Jonathan Enroth, Stefan Kerr, Shona M Surakka, Ida Vitart, Veronique Lehtimäki, Terho Allen, Richard J Bakke, Per S Beaty, Terri H Bleecker, Eugene R Bossé, Yohan Brandsma, Corry-Anke Chen, Zhengming Crapo, James D Danesh, John DeMeo, Dawn L Dudbridge, Frank Ewert, Ralf Gieger, Christian Gulsvik, Amund Hansell, Anna L Hao, Ke Hoffman, Joshua D Hokanson, John E Homuth, Georg Joshi, Peter K Joubert, Philippe Langenberg, Claudia Li, Xuan Li, Liming Lin, Kuang Lind, Lars Locantore, Nicholas Luan, Jian’an Mahajan, Anubha Maranville, Joseph C Murray, Alison Nickle, David C Packer, Richard Parker, Margaret M Paynton, Megan L Porteous, David J Prokopenko, Dmitry Qiao, Dandi Rawal, Rajesh Runz, Heiko Sayers, Ian Sin, Don D Smith, Blair H Artigas, María Soler Sparrow, David Tal-Singer, Ruth Timmers, Paul RHJ Van den Berge, Maarten Whittaker, John C Woodruff, Prescott G Yerges-Armstrong, Laura M Troyanskaya, Olga G Raitakari, Olli T Kähönen, Mika Polasek, Ozren Gyllensten, Ulf Rudan, Igor Deary, Ian J Probst-Hensch, Nicole M Schulz, Holger James, Alan L Wilson, James F Stubbe, Beate Zeggini, Eleftheria Jarvelin, Marjo-Riitta Wareham, Nick Silverman, Edwin K Hayward, Caroline Morris, Andrew P Butterworth, Adam S Scott, Robert A Walters, Robin G Meyers, Deborah A Cho, Michael H Strachan, David P Hall, Ian P Tobin, Martin D Wain, Louise V |
author_sort | Shrine, Nick |
collection | PubMed |
description | 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 patient 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. |
format | Online Article Text |
id | pubmed-6397078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-63970782019-08-25 New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. Shrine, Nick Guyatt, Anna L Erzurumluoglu, A Mesut Jackson, Victoria E Hobbs, Brian D Melbourne, Carl A Batini, Chiara Fawcett, Katherine A Song, Kijoung Sakornsakolpat, Phuwanat Li, Xingnan Boxall, Ruth Reeve, Nicola F Obeidat, Ma’en Zhao, Jing Hua Wielscher, Matthias Weiss, Stefan Kentistou, Katherine A Cook, James P Sun, Benjamin B Zhou, Jian Hui, Jennie Karrasch, Stefan Imboden, Medea Harris, Sarah E Marten, Jonathan Enroth, Stefan Kerr, Shona M Surakka, Ida Vitart, Veronique Lehtimäki, Terho Allen, Richard J Bakke, Per S Beaty, Terri H Bleecker, Eugene R Bossé, Yohan Brandsma, Corry-Anke Chen, Zhengming Crapo, James D Danesh, John DeMeo, Dawn L Dudbridge, Frank Ewert, Ralf Gieger, Christian Gulsvik, Amund Hansell, Anna L Hao, Ke Hoffman, Joshua D Hokanson, John E Homuth, Georg Joshi, Peter K Joubert, Philippe Langenberg, Claudia Li, Xuan Li, Liming Lin, Kuang Lind, Lars Locantore, Nicholas Luan, Jian’an Mahajan, Anubha Maranville, Joseph C Murray, Alison Nickle, David C Packer, Richard Parker, Margaret M Paynton, Megan L Porteous, David J Prokopenko, Dmitry Qiao, Dandi Rawal, Rajesh Runz, Heiko Sayers, Ian Sin, Don D Smith, Blair H Artigas, María Soler Sparrow, David Tal-Singer, Ruth Timmers, Paul RHJ Van den Berge, Maarten Whittaker, John C Woodruff, Prescott G Yerges-Armstrong, Laura M Troyanskaya, Olga G Raitakari, Olli T Kähönen, Mika Polasek, Ozren Gyllensten, Ulf Rudan, Igor Deary, Ian J Probst-Hensch, Nicole M Schulz, Holger James, Alan L Wilson, James F Stubbe, Beate Zeggini, Eleftheria Jarvelin, Marjo-Riitta Wareham, Nick Silverman, Edwin K Hayward, Caroline Morris, Andrew P Butterworth, Adam S Scott, Robert A Walters, Robin G Meyers, Deborah A Cho, Michael H Strachan, David P Hall, Ian P Tobin, Martin D Wain, Louise V Nat Genet Article 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 patient 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. 2019-02-25 2019-03 /pmc/articles/PMC6397078/ /pubmed/30804560 http://dx.doi.org/10.1038/s41588-018-0321-7 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Shrine, Nick Guyatt, Anna L Erzurumluoglu, A Mesut Jackson, Victoria E Hobbs, Brian D Melbourne, Carl A Batini, Chiara Fawcett, Katherine A Song, Kijoung Sakornsakolpat, Phuwanat Li, Xingnan Boxall, Ruth Reeve, Nicola F Obeidat, Ma’en Zhao, Jing Hua Wielscher, Matthias Weiss, Stefan Kentistou, Katherine A Cook, James P Sun, Benjamin B Zhou, Jian Hui, Jennie Karrasch, Stefan Imboden, Medea Harris, Sarah E Marten, Jonathan Enroth, Stefan Kerr, Shona M Surakka, Ida Vitart, Veronique Lehtimäki, Terho Allen, Richard J Bakke, Per S Beaty, Terri H Bleecker, Eugene R Bossé, Yohan Brandsma, Corry-Anke Chen, Zhengming Crapo, James D Danesh, John DeMeo, Dawn L Dudbridge, Frank Ewert, Ralf Gieger, Christian Gulsvik, Amund Hansell, Anna L Hao, Ke Hoffman, Joshua D Hokanson, John E Homuth, Georg Joshi, Peter K Joubert, Philippe Langenberg, Claudia Li, Xuan Li, Liming Lin, Kuang Lind, Lars Locantore, Nicholas Luan, Jian’an Mahajan, Anubha Maranville, Joseph C Murray, Alison Nickle, David C Packer, Richard Parker, Margaret M Paynton, Megan L Porteous, David J Prokopenko, Dmitry Qiao, Dandi Rawal, Rajesh Runz, Heiko Sayers, Ian Sin, Don D Smith, Blair H Artigas, María Soler Sparrow, David Tal-Singer, Ruth Timmers, Paul RHJ Van den Berge, Maarten Whittaker, John C Woodruff, Prescott G Yerges-Armstrong, Laura M Troyanskaya, Olga G Raitakari, Olli T Kähönen, Mika Polasek, Ozren Gyllensten, Ulf Rudan, Igor Deary, Ian J Probst-Hensch, Nicole M Schulz, Holger James, Alan L Wilson, James F Stubbe, Beate Zeggini, Eleftheria Jarvelin, Marjo-Riitta Wareham, Nick Silverman, Edwin K Hayward, Caroline Morris, Andrew P Butterworth, Adam S Scott, Robert A Walters, Robin G Meyers, Deborah A Cho, Michael H Strachan, David P Hall, Ian P Tobin, Martin D Wain, Louise V New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. |
title | New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. |
title_full | New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. |
title_fullStr | New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. |
title_full_unstemmed | New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. |
title_short | New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. |
title_sort | new genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397078/ https://www.ncbi.nlm.nih.gov/pubmed/30804560 http://dx.doi.org/10.1038/s41588-018-0321-7 |
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