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dc.contributor.authorGilly, Arthur
dc.contributor.authorPark, Young-Chan
dc.contributor.authorPng, Grace
dc.contributor.authorBarysenka, Andrei
dc.contributor.authorFischer, Iris
dc.contributor.authorBjørnland, Thea
dc.contributor.authorSoutham, Lorraine
dc.contributor.authorSuveges, Daniel
dc.contributor.authorNeumeyer, Sonja
dc.contributor.authorRayner, N William
dc.contributor.authorTsafantakis, Emmanouil
dc.contributor.authorKaraleftheri, Maria
dc.contributor.authorDedoussis, George
dc.contributor.authorZeggini, Eleftheria
dc.date.accessioned2020-12-10T16:21:47Z
dc.date.available2020-12-10T16:21:47Z
dc.date.issued2020-12-10
dc.date.submitted2020-04-07
dc.identifier.issn2041-1723
dc.identifier.others41467-020-20079-2
dc.identifier.other20079
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/314966
dc.description.abstractThe human proteome is a crucial intermediate between complex diseases and their genetic and environmental components, and an important source of drug development targets and biomarkers. Here, we comprehensively assess the genetic architecture of 257 circulating protein biomarkers of cardiometabolic relevance through high-depth (22.5×) whole-genome sequencing (WGS) in 1328 individuals. We discover 131 independent sequence variant associations (P < 7.45 × 10-11) across the allele frequency spectrum, all of which replicate in an independent cohort (n = 1605, 18.4x WGS). We identify for the first time replicating evidence for rare-variant cis-acting protein quantitative trait loci for five genes, involving both coding and noncoding variation. We construct and validate polygenic scores that explain up to 45% of protein level variation. We find causal links between protein levels and disease risk, identifying high-value biomarkers and drug development targets.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectArticle
dc.subject/631/208/514/2254
dc.subject/631/337/475
dc.subject/692/53
dc.subject/45
dc.subjectarticle
dc.titleWhole-genome sequencing analysis of the cardiometabolic proteome.
dc.typeArticle
dc.date.updated2020-12-10T16:21:46Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume11
dc.identifier.doi10.17863/CAM.62073
dcterms.dateAccepted2020-10-26
rioxxterms.versionofrecord10.1038/s41467-020-20079-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidFischer, Iris [0000-0002-5080-1223]
dc.contributor.orcidZeggini, Eleftheria [0000-0003-4238-659X]
dc.identifier.eissn2041-1723
pubs.funder-project-idWellcome Trust (Wellcome) (098051)
cam.issuedOnline2020-12-10


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)