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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

Wain, Louise V.; Shrine, Nick; Artigas, Mar�a Soler; Erzurumluoglu, A. Mesut; Noyvert, Boris; Bossini-Castillo, Lara; Obeidat, Ma�en; Henry, Amanda P.; Portelli, Michael A.; Hall, Robert J.; Billington, Charlotte K.; Rimington, Tracy L.; Fenech, Anthony G.; Johnson, Catherine; Blake, Tineka; Jackson, Victoria E.; Allen, Richard J.; Prins, Bram P.; Campbell, Archie; Sayers, Ian; Hall, Ian P.

Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets Thumbnail


Authors

Louise V. Wain

Nick Shrine

Mar�a Soler Artigas

A. Mesut Erzurumluoglu

Boris Noyvert

Lara Bossini-Castillo

Ma�en Obeidat

Amanda P. Henry

Michael A. Portelli

Robert J. Hall

Charlotte K. Billington

Tracy L. Rimington

Anthony G. Fenech

Catherine Johnson

Tineka Blake

Victoria E. Jackson

Richard J. Allen

Bram P. Prins

Archie Campbell

Ian P. Hall



Abstract

Chronic obstructive pulmonary disease (COPD) is characterized 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 ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20–1.27), P = 5.05 × 10−49), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers 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.

Journal Article Type Article
Acceptance Date Jan 13, 2017
Online Publication Date Feb 6, 2017
Publication Date 2017-03
Deposit Date Apr 3, 2017
Publicly Available Date Apr 3, 2017
Journal Nature Genetics
Print ISSN 1061-4036
Electronic ISSN 1546-1718
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 49
Issue 3
Pages 416-425
DOI https://doi.org/10.1038/ng.3787
Keywords Genetics research, Genome-wide association studies, Respiratory tract diseases
Public URL https://nottingham-repository.worktribe.com/output/847487
Publisher URL http://www.nature.com/ng/journal/v49/n3/full/ng.3787.html
Additional Information 106 authors and 2 corporate authors.

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