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

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.

SUBMITTER: Shrine N 

PROVIDER: S-EPMC6397078 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Shrine Nick N   Guyatt Anna L AL   Erzurumluoglu A Mesut AM   Jackson Victoria E VE   Hobbs Brian D BD   Melbourne Carl A CA   Batini Chiara C   Fawcett Katherine A KA   Song Kijoung K   Sakornsakolpat Phuwanat P   Li Xingnan X   Boxall Ruth R   Reeve Nicola F NF   Obeidat Ma'en M   Zhao Jing Hua JH   Wielscher Matthias M   Weiss Stefan S   Kentistou Katherine A KA   Kentistou Katherine A KA   Cook James P JP   Sun Benjamin B BB   Zhou Jian J   Hui Jennie J   Karrasch Stefan S   Imboden Medea M   Harris Sarah E SE   Marten Jonathan J   Enroth Stefan S   Kerr Shona M SM   Surakka Ida I   Vitart Veronique V   Lehtimäki Terho T   Allen Richard J RJ   Bakke Per S PS   Beaty Terri H TH   Bleecker Eugene R ER   Bossé Yohan Y   Brandsma Corry-Anke CA   Chen Zhengming Z   Crapo James D JD   Danesh John J   DeMeo Dawn L DL   Dudbridge Frank F   Ewert Ralf R   Gieger Christian C   Gulsvik Amund A   Hansell Anna L AL   Hao Ke K   Hoffman Joshua D JD   Hokanson John E JE   Homuth Georg G   Joshi Peter K PK   Joubert Philippe P   Langenberg Claudia C   Li Xuan X   Li Liming L   Lin Kuang K   Lind Lars L   Locantore Nicholas N   Luan Jian'an J   Mahajan Anubha A   Maranville Joseph C JC   Murray Alison A   Nickle David C DC   Packer Richard R   Parker Margaret M MM   Paynton Megan L ML   Porteous David J DJ   Porteous David J DJ   Prokopenko Dmitry D   Qiao Dandi D   Rawal Rajesh R   Runz Heiko H   Sayers Ian I   Sin Don D DD   Smith Blair H BH   Soler Artigas María M   Sparrow David D   Tal-Singer Ruth R   Timmers Paul R H J PRHJ   Van den Berge Maarten M   Whittaker John C JC   Woodruff Prescott G PG   Yerges-Armstrong Laura M LM   Troyanskaya Olga G OG   Raitakari Olli T OT   Kähönen Mika M   Polašek Ozren O   Gyllensten Ulf U   Rudan Igor I   Deary Ian J IJ   Probst-Hensch Nicole M NM   Schulz Holger H   James Alan L AL   Wilson James F JF   Stubbe Beate B   Zeggini Eleftheria E   Jarvelin Marjo-Riitta MR   Wareham Nick N   Silverman Edwin K EK   Hayward Caroline C   Morris Andrew P AP   Butterworth Adam S AS   Scott Robert A RA   Walters Robin G RG   Meyers Deborah A DA   Cho Michael H MH   Strachan David P DP   Hall Ian P IP   Tobin Martin D MD   Wain Louise V LV  

Nature genetics 20190225 3

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  ...[more]

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