New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.
; Guyatt, Anna L; Erzurumluoglu, A Mesut; Jackson, Victoria E; Hobbs, Brian D; Melbourne, Carl A; Batini, Chiara; Fawcett, Katherine A; Song, Kijoung; Sakornsakolpat, Phuwanat; +100 more...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; Soler Artigas, María; 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; Polašek, 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; and Understanding Society Scientific Group
(2019)
New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.
NATURE GENETICS, 51 (3).
pp. 481-493.
ISSN 1061-4036
DOI: 10.1038/s41588-018-0321-7
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.
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