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dc.contributor.authorYao, Chen
dc.contributor.authorChen, George
dc.contributor.authorSong, Ci
dc.contributor.authorKeefe, Joshua
dc.contributor.authorMendelson, Michael
dc.contributor.authorHuan, Tianxiao
dc.contributor.authorSun, Benjamin B
dc.contributor.authorLaser, Annika
dc.contributor.authorMaranville, Joseph C
dc.contributor.authorWu, Hongsheng
dc.contributor.authorHo, Jennifer E
dc.contributor.authorCourchesne, Paul
dc.contributor.authorLyass, Asya
dc.contributor.authorLarson, Martin G
dc.contributor.authorGieger, Christian
dc.contributor.authorGraumann, Johannes
dc.contributor.authorJohnson, Andrew D
dc.contributor.authorDanesh, John
dc.contributor.authorRunz, Heiko
dc.contributor.authorHwang, Shih-Jen
dc.contributor.authorLiu, Chunyu
dc.contributor.authorButterworth, Adam S
dc.contributor.authorSuhre, Karsten
dc.contributor.authorLevy, Daniel
dc.date.accessioned2018-11-13T00:31:33Z
dc.date.available2018-11-13T00:31:33Z
dc.date.issued2018-08-15
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284992
dc.description.abstractIdentifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome's causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in 6861 Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectCardiovascular Diseases
dc.subjectGenetic Predisposition to Disease
dc.subjectBlood Proteins
dc.subjectRisk Factors
dc.subjectChromosome Mapping
dc.subjectGene Expression Profiling
dc.subjectSignal Transduction
dc.subjectPolymorphism, Single Nucleotide
dc.subjectQuantitative Trait Loci
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.titleGenome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameNat Commun
prism.startingPage3268
prism.volume9
dc.identifier.doi10.17863/CAM.32363
dcterms.dateAccepted2018-07-09
rioxxterms.versionofrecord10.1038/s41467-018-05512-x
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08-15
dc.contributor.orcidYao, Chen [0000-0002-3944-7788]
dc.contributor.orcidSun, Benjamin B [0000-0001-6347-2281]
dc.contributor.orcidGraumann, Johannes [0000-0002-3015-5850]
dc.contributor.orcidButterworth, Adam S [0000-0002-6915-9015]
dc.contributor.orcidSuhre, Karsten [0000-0001-9638-3912]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idEuropean Research Council (268834)
pubs.funder-project-idMedical Research Council (G0800270)
pubs.funder-project-idBritish Heart Foundation (None)
cam.issuedOnline2018-08-15


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