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dc.contributor.authorNurnberg, Sylvia T
dc.contributor.authorGuerraty, Marie A
dc.contributor.authorWirka, Robert C
dc.contributor.authorRao, H Shanker
dc.contributor.authorPjanic, Milos
dc.contributor.authorNorton, Scott
dc.contributor.authorSerrano, Felipe
dc.contributor.authorPerisic, Ljubica
dc.contributor.authorElwyn, Susannah
dc.contributor.authorPluta, John
dc.contributor.authorZhao, Wei
dc.contributor.authorTesta, Stephanie
dc.contributor.authorPark, YoSon
dc.contributor.authorNguyen, Trieu
dc.contributor.authorKo, Yi-An
dc.contributor.authorWang, Ting
dc.contributor.authorHedin, Ulf
dc.contributor.authorSinha, Sanjay
dc.contributor.authorBarash, Yoseph
dc.contributor.authorBrown, Christopher D
dc.contributor.authorQuertermous, Thomas
dc.contributor.authorRader, Daniel J
dc.date.accessioned2019-11-29T00:30:49Z
dc.date.available2019-11-29T00:30:49Z
dc.date.issued2020-01
dc.identifier.issn1553-7390
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/299435
dc.description.abstractGenome-wide association studies have identified multiple novel genomic loci associated with vascular diseases. Many of these loci are common non-coding variants that affect the expression of disease-relevant genes within coronary vascular cells. To identify such genes on a genome-wide level, we performed deep transcriptomic analysis of genotyped primary human coronary artery smooth muscle cells (HCASMCs) and coronary endothelial cells (HCAECs) from the same subjects, including splicing Quantitative Trait Loci (sQTL), allele-specific expression (ASE), and colocalization analyses. We identified sQTLs for TARS2, YAP1, CFDP1, and STAT6 in HCASMCs and HCAECs, and 233 ASE genes, a subset of which are also GTEx eGenes in arterial tissues. Colocalization of GWAS association signals for coronary artery disease (CAD), migraine, stroke and abdominal aortic aneurysm with GTEx eGenes in aorta, coronary artery and tibial artery discovered novel candidate risk genes for these diseases. At the CAD and stroke locus tagged by rs2107595 we demonstrate colocalization with expression of the proximal gene TWIST1. We show that disrupting the rs2107595 locus alters TWIST1 expression and that the risk allele has increased binding of the NOTCH signaling protein RBPJ. Finally, we provide data that TWIST1 expression influences vascular SMC phenotypes, including proliferation and calcification, as a potential mechanism supporting a role for TWIST1 in CAD.
dc.format.mediumElectronic-eCollection
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCoronary Vessels
dc.subjectEndothelium, Vascular
dc.subjectCells, Cultured
dc.subjectEndothelial Cells
dc.subjectMyocytes, Smooth Muscle
dc.subjectHumans
dc.subjectVascular Diseases
dc.subjectNuclear Proteins
dc.subjectProtein Binding
dc.subjectPolymorphism, Single Nucleotide
dc.subjectImmunoglobulin J Recombination Signal Sequence-Binding Protein
dc.subjectTranscriptome
dc.subjectTwist-Related Protein 1
dc.titleGenomic profiling of human vascular cells identifies TWIST1 as a causal gene for common vascular diseases.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2020
prism.publicationNamePLoS Genet
prism.startingPagee1008538
prism.volume16
dc.identifier.doi10.17863/CAM.46504
dcterms.dateAccepted2019-11-25
rioxxterms.versionofrecord10.1371/journal.pgen.1008538
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-01-09
dc.contributor.orcidNurnberg, Sylvia T [0000-0002-0869-484X]
dc.contributor.orcidGuerraty, Marie A [0000-0002-0766-1253]
dc.contributor.orcidWirka, Robert C [0000-0001-9131-9508]
dc.contributor.orcidRao, H Shanker [0000-0001-6827-1470]
dc.contributor.orcidNorton, Scott [0000-0002-1366-0628]
dc.contributor.orcidPluta, John [0000-0002-8941-6242]
dc.contributor.orcidZhao, Wei [0000-0002-8301-9297]
dc.contributor.orcidPark, YoSon [0000-0002-0465-4744]
dc.contributor.orcidNguyen, Trieu [0000-0001-5647-1301]
dc.contributor.orcidHedin, Ulf [0000-0001-9212-3945]
dc.contributor.orcidBarash, Yoseph [0000-0003-3005-5048]
dc.contributor.orcidBrown, Christopher D [0000-0002-3785-5008]
dc.contributor.orcidQuertermous, Thomas [0000-0002-7645-9067]
dc.contributor.orcidRader, Daniel J [0000-0002-9245-9876]
dc.identifier.eissn1553-7404
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBritish Heart Foundation (RG/17/5/32936)
pubs.funder-project-idMedical Research Council (MC_PC_12009)
pubs.funder-project-idBritish Heart Foundation (FS/18/46/33663)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
cam.issuedOnline2020-01-09
cam.orpheus.successMon Jun 08 08:21:46 BST 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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