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

Authors:
Nick Shrine Anna L Guyatt A Mesut Erzurumluoglu Victoria E Jackson Brian D Hobbs Carl A 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 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 Joshua D Hoffman John E Hokanson Georg Homuth Peter K Joshi Philippe Joubert Claudia Langenberg Xuan Li Liming Li Kuang Lin Lars Lind Nicholas Locantore Jian'an Luan Anubha Mahajan Joseph C Maranville Alison Murray David C Nickle Richard Packer Margaret M Parker Megan L Paynton David J 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 R H J Timmers Maarten Van den Berge John C Whittaker Prescott G Woodruff Laura M Yerges-Armstrong Olga G Troyanskaya Olli T Raitakari Mika Kähönen Ozren Polašek 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

Nat Genet 2019 03 25;51(3):481-493. Epub 2019 Feb 25.

Department of Health Sciences, University of Leicester, Leicester, UK.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-018-0321-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397078PMC
March 2019
33 Reads
29.352 Impact Factor

Publication Analysis

Top Keywords

lung function
12
pulmonary disease
8
obstructive pulmonary
8
chronic obstructive
8
variants generalizability
4
combined variants
4
generalizability smokers
4
smokers ancestral
4
highlight biological
4
biological pathways
4
groups highlight
4
ancestral groups
4
populations combined
4
smokers smokers
4
independent populations
4
279 lung
4
define 279
4
ancestry define
4
european ancestry
4
function signals
4

Similar Publications