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New genetic signals for lung function highlight pathways and pleiotropy, and chronic obstructive pulmonary disease associations across multiple ancestries
By
Nick Shrine,
Anna L Guyatt,
A Mesut Erzurumluoglu,
Victoria E Jackson,
Brian D. Hobbs,
Carl 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,
Understanding Society Scientific Group,
Stefan Weiss,
Katherine A Kentistou,
James P Cook,
Benjamin 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,
Josh D Hoffman,
John Hokanson,
Georg Homuth,
Peter K Joshi,
Philippe Joubert,
Claudia Langenberg,
Xuan Li,
Liming Li,
Kuang Lin,
Lars Lind,
Nick Locantore,
Jian’an Luan,
Anubha Mahajan,
Joseph C. Maranville,
Alison Murray,
David C Nickle,
Richard Packer,
Margaret M Parker,
Megan L Paynton,
David Porteous,
Dmitry Prokopenko,
Dandi Qiao,
Rajesh Rawal,
Heiko Runz,
Ian Sayers,
Don D. Sin,
Blair H Smith,
María Soler Artigas,
David Sparrow,
Ruth Tal-Singer,
Paul RHJ Timmers,
Maarten Van den Berge,
John C Whittaker,
Prescott Woodruff,
Laura M Yerges Armstrong,
Olga G Troyanskaya,
Olli T Raitakari,
Mika Kähönen,
Ozren Polasek,
Ulf Gyllensten,
Igor Rudan,
Ian J Deary,
Nicole M Probst-Hensch,
Holger Schulz,
Alan L James,
James F Wilson,
Beate Stubbe,
Eleftheria Zeggini,
Marjo-Riitta Jarvelin,
Nick Wareham,
Edwin K Silverman,
Caroline Hayward,
Andrew P Morris,
Adam S. Butterworth,
Robert A Scott,
Robin G Walters,
Deborah A Meyers,
Michael H Cho,
David P Strachan,
Ian P Hall,
Martin D Tobin,
Louise V Wain
Posted 12 Jun 2018
bioRxiv DOI: 10.1101/343293
(published DOI: 10.1038/s41588-018-0321-7)
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.
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