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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.accessioned2020-01-23T02:14:43Z
dc.date.available2020-01-23T02:14:43Z
dc.date.issued2020-01-09
dc.date.submitted2019-03-11
dc.identifier.issn1553-7390
dc.identifier.otherpgenetics-d-19-00403
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/301185
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.languageen
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectMedicine and health sciences
dc.subjectBiology and life sciences
dc.titleGenomic profiling of human vascular cells identifies TWIST1 as a causal gene for common vascular diseases
dc.typeArticle
dc.date.updated2020-01-23T02:14:42Z
dc.identifier.doi10.17863/CAM.48263
dcterms.dateAccepted2019-11-25
rioxxterms.versionofrecord10.1371/journal.pgen.1008538
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Chasman, Daniel I
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


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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)