Publication type
Journal Article
Authors
- Louise V. Wain
- Nick Shrine
- María Soler Artigas
- A. Mesut Erzurumluoglu
- Boris Noyvert
- L. Bossini-Castillo
- M. Obeidat
- A. P. Henry
- M. A . Portelli
- R. J. Hall
- C. K. Billington
- T. L. Rimington
- A. G. Fenech
- Catherine John
- Tineka Blake
- Victoria E. Jackson
- Richard J. Allen
- B. P. Prins
- A. Campbell
- D. J. Porteous
- M.-R. Jarvelin
- M. Wielscher
- A. L. James
- J. Hui
- N. J Wareham
- J. H. Zhao
- J. F. Wilson
- P. K. Joshi
- B. Stubbe
- R. Rawal
- H. Schulz
- M. Imboden
- N. M. Probst-Hensch
- S. Karrasch
- C. Gieger
- I. J. Deary
- S. E. Harris
- J. Marten
- I. Rudan
- S. Enroth
- U. Gyllensten
- S. M. Kerr
- O. Polasek
- M. Kähönen
- I. Surakka
- V. Vitart
- C. Hayward
- T. Lehtimäki
- O. Raitakari
- D. M. Evans
- A. J. Henderson
- C. E. Pennell
- C. A. Wang
- P. D. Sly
- E. S. Wan
- R. Busch
- B. D. Hobbs
- A. A. Litonjua
- D. W. Sparrow
- A. Gulsvik
- P. S. Bakke
- J. D. Crapo
- T. H. Beaty
- N. N. Hansel
- R. A. Mathias
- I. Ruczinski
- K. C. Barnes
- Y. Bossé
- P. Joubert
- M. van den Berge
- C. -A. Brandsma
- P. D. Paré
- D. D. Sin
- D. C. Nickle
- K. Hao
- O. Gottesman
- F. E. Dewey
- S. E. Bruse
- D. J. Carey
- H. L. Kirchner
- S. Jonsson
- G. Thorleifsson
- I. Jonsdottir
- T. Gislason
- K. Stefansson
- C. Schurmann
- G. Nadkarni
- E. P. Bottinger
- R. J. F. Loos
- R. G. Walters
- Z. Chen
- I. Y. Millwood
- J. Vaucher
- O. P. Kurmi
- L. Li
- A. L. Hansell
- Chris Brightling
- E. Zeggini
- M. H. Cho
- E. K. Silverman
- I. Sayers
- G. Trynka
- A. P. Morris
- D. P. Strachan
- I. P. Hall
- Martin D. Tobin
Publication date
February 15, 2017
Summary:
Chronic Obstructive Pulmonary Disease (COPD) is characterised by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratios per standard deviation of the risk score (~6 alleles) (95% confidence interval) 1.24 (1.20-1.27), P=5.05x10^-49) and we observed a 3.7 fold difference in COPD risk between highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in development, elastic fibres and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
Published in
Nature Genetics
Volume and page numbers
Volume: 49 , p.416 -425
DOI
http://dx.doi.org/10.1038/ng.3787
ISSN
10614036
Subjects
#524114