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dc.contributor.authorWain, LVen
dc.contributor.authorShrine, Nen
dc.contributor.authorArtigas, MSen
dc.contributor.authorErzurumluoglu, AMen
dc.contributor.authorNoyvert, Ben
dc.contributor.authorBossini-Castillo, Len
dc.contributor.authorObeidat, Men
dc.contributor.authorHenry, APen
dc.contributor.authorPortelli, MAen
dc.contributor.authorHall, RJen
dc.contributor.authorBillington, CKen
dc.contributor.authorRimington, TLen
dc.contributor.authorFenech, AGen
dc.contributor.authorJohn, Cen
dc.contributor.authorBlake, Ten
dc.contributor.authorJackson, VEen
dc.contributor.authorAllen, RJen
dc.contributor.authorPrins, Bramen
dc.contributor.authorUnderstanding Society Scientific Group,en
dc.contributor.authorCampbell, Aen
dc.contributor.authorPorteous, DJen
dc.contributor.authorJarvelin, M-Ren
dc.contributor.authorWielscher, Men
dc.contributor.authorJames, ALen
dc.contributor.authorHui, Jen
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorZhao, Jing Huaen
dc.contributor.authorWilson, JFen
dc.contributor.authorJoshi, PKen
dc.contributor.authorStubbe, Ben
dc.contributor.authorRawal, Ren
dc.contributor.authorSchulz, Hen
dc.contributor.authorImboden, Men
dc.contributor.authorProbst-Hensch, NMen
dc.contributor.authorKarrasch, Sen
dc.contributor.authorGieger, Cen
dc.contributor.authorDeary, IJen
dc.contributor.authorHarris, SEen
dc.contributor.authorMarten, Jonathanen
dc.contributor.authorRudan, Ien
dc.contributor.authorEnroth, Sen
dc.contributor.authorGyllensten, Uen
dc.contributor.authorKerr, SMen
dc.contributor.authorPolasek, Oen
dc.contributor.authorKähönen, Men
dc.contributor.authorSurakka, Ien
dc.contributor.authorVitart, Ven
dc.contributor.authorHayward, Cen
dc.contributor.authorLehtimäki, Ten
dc.contributor.authorRaitakari, OTen
dc.contributor.authorEvans, DMen
dc.contributor.authorHenderson, AJen
dc.contributor.authorPennell, CEen
dc.contributor.authorWang, CAen
dc.contributor.authorSly, PDen
dc.contributor.authorWan, ESen
dc.contributor.authorBusch, Ren
dc.contributor.authorHobbs, BDen
dc.contributor.authorLitonjua, AAen
dc.contributor.authorSparrow, DWen
dc.contributor.authorGulsvik, Aen
dc.contributor.authorBakke, PSen
dc.contributor.authorCrapo, JDen
dc.contributor.authorBeaty, THen
dc.contributor.authorHansel, NNen
dc.contributor.authorMathias, RAen
dc.contributor.authorRuczinski, Ien
dc.contributor.authorBarnes, KCen
dc.contributor.authorBossé, Yen
dc.contributor.authorJoubert, Pen
dc.contributor.authorvan den Berge, Men
dc.contributor.authorBrandsma, C-Aen
dc.contributor.authorParé, PDen
dc.contributor.authorSin, DDen
dc.contributor.authorNickle, DCen
dc.contributor.authorHao, Ken
dc.contributor.authorGottesman, Oen
dc.contributor.authorDewey, FEen
dc.contributor.authorBruse, SEen
dc.contributor.authorCarey, DJen
dc.contributor.authorKirchner, HLen
dc.contributor.authorGeisinger-Regeneron DiscovEHR Collaboration,en
dc.contributor.authorJonsson, Sen
dc.contributor.authorThorleifsson, Gen
dc.contributor.authorJonsdottir, Ien
dc.contributor.authorGislason, Ten
dc.contributor.authorStefansson, Ken
dc.contributor.authorSchurmann, Cen
dc.contributor.authorNadkarni, Gen
dc.contributor.authorBottinger, EPen
dc.contributor.authorLoos, RJFen
dc.contributor.authorWalters, RGen
dc.contributor.authorChen, Zen
dc.contributor.authorMillwood, IYen
dc.contributor.authorVaucher, Jen
dc.contributor.authorKurmi, OPen
dc.contributor.authorLi, Len
dc.contributor.authorHansell, ALen
dc.contributor.authorBrightling, Cen
dc.contributor.authorZeggini, Een
dc.contributor.authorCho, MHen
dc.contributor.authorSilverman, EKen
dc.contributor.authorSayers, Ien
dc.contributor.authorTrynka, Gen
dc.contributor.authorMorris, APen
dc.contributor.authorStrachan, DPen
dc.contributor.authorHall, IPen
dc.contributor.authorTobin, MDen
dc.date.accessioned2017-04-03T13:16:22Z
dc.date.available2017-04-03T13:16:22Z
dc.date.issued2017-03en
dc.identifier.issn1061-4036
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/263444
dc.description.abstractChronic 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.
dc.description.sponsorshipThis work was funded by a Medical Research Council (MRC) strategic award to M.D.T., I.P.H., D.S. and L.V.W. (MC_PC_12010). This research has been conducted using the UK Biobank Resource under application 648. This article presents independent research funded partially by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the UK Department of Health. This research used the ALICE and SPECTRE High-Performance Computing Facilities at the University of Leicester. Additional acknowledgments and funding details can be found in the Supplementary Note.
dc.languageengen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.titleGenome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targetsen
dc.typeArticle
prism.endingPage425
prism.issueIdentifier3en
prism.publicationDate2017en
prism.publicationNameNature Geneticsen
prism.startingPage416
prism.volume49en
dc.identifier.doi10.17863/CAM.8791
dcterms.dateAccepted2017-01-13en
rioxxterms.versionofrecord10.1038/ng.3787en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-03en
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidZhao, Jing Hua [0000-0003-4930-3582]
dc.contributor.orcidMarten, Jonathan [0000-0001-6916-2014]
dc.identifier.eissn1546-1718
rioxxterms.typeJournal Article/Reviewen
cam.issuedOnline2017-02-06en
rioxxterms.freetoread.startdate2017-08-06


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