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

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Serval ID
serval:BIB_E3ED27216D2C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Production externe
Title
Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
Journal
Nature genetics
Author(s)
Wain L.V., Shrine N., Artigas M.S., Erzurumluoglu A.M., Noyvert B., Bossini-Castillo L., Obeidat M., Henry A.P., Portelli M.A., Hall R.J., Billington C.K., Rimington T.L., Fenech A.G., John C., Blake T., Jackson V.E., Allen R.J., Prins B.P., Campbell A., Porteous D.J., Jarvelin M.R., Wielscher M., James A.L., Hui J., Wareham N.J., Zhao J.H., Wilson J.F., Joshi P.K., Stubbe B., Rawal R., Schulz H., Imboden M., Probst-Hensch N.M., Karrasch S., Gieger C., Deary I.J., Harris S.E., Marten J., Rudan I., Enroth S., Gyllensten U., Kerr S.M., Polasek O., Kähönen M., Surakka I., Vitart V., Hayward C., Lehtimäki T., Raitakari O.T., Evans D.M., Henderson A.J., Pennell C.E., Wang C.A., Sly P.D., Wan E.S., Busch R., Hobbs B.D., Litonjua A.A., Sparrow D.W., Gulsvik A., Bakke P.S., Crapo J.D., Beaty T.H., Hansel N.N., Mathias R.A., Ruczinski I., Barnes K.C., Bossé Y., Joubert P., van den Berge M., Brandsma C.A., Paré P.D., Sin D.D., Nickle D.C., Hao K., Gottesman O., Dewey F.E., Bruse S.E., Carey D.J., Kirchner H.L., Jonsson S., Thorleifsson G., Jonsdottir I., Gislason T., Stefansson K., Schurmann C., Nadkarni G., Bottinger E.P., Loos R.J., Walters R.G., Chen Z., Millwood I.Y., Vaucher J., Kurmi O.P., Li L., Hansell A.L., Brightling C., Zeggini E., Cho M.H., Silverman E.K., Sayers I., Trynka G., Morris A.P., Strachan D.P., Hall I.P., Tobin M.D.
Working group(s)
Understanding Society Scientific Group, Geisinger-Regeneron DiscovEHR Collaboration
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
03/2017
Peer-reviewed
Oui
Volume
49
Number
3
Pages
416-425
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.

DOI
10.1038/ng.3787
Pubmed
28166213
Web of science
000394917800015
Create date
07/02/2017 12:28
Last modification date
20/08/2019 16:07
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