Show simple item record

dc.contributor.authorBeaney, Katherine Een
dc.contributor.authorSmith, Andrew JPen
dc.contributor.authorFolkersen, Lasseen
dc.contributor.authorPalmen, Juttaen
dc.contributor.authorWannamethee, S Goyaen
dc.contributor.authorJefferis, Barbara Jen
dc.contributor.authorWhincup, Peteren
dc.contributor.authorGaunt, Tom Ren
dc.contributor.authorCasas, Juan Pen
dc.contributor.authorBen-Shlomo, Yoaven
dc.contributor.authorPrice, Jacqueline Fen
dc.contributor.authorKumari, Meenaen
dc.contributor.authorWong, Andrewen
dc.contributor.authorOng, Kennethen
dc.contributor.authorHardy, Rebeccaen
dc.contributor.authorKuh, Dianaen
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorKivimaki, Mikaen
dc.contributor.authorEriksson, Peren
dc.contributor.authorHumphries, Steve Een
dc.contributor.authorConsortium, Ucleben
dc.date.accessioned2017-08-16T12:39:42Z
dc.date.available2017-08-16T12:39:42Z
dc.date.issued2017-01en
dc.identifier.issn0278-0240
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/266508
dc.description.abstractBackground. The coronary heart disease (CHD) risk locus on 21q22 (lead SNP rs9982601) lies within a "gene desert." The aim of this study was to assess if this locus is associated with CHD risk factors and to identify the functional variant(s) and gene(s) involved. Methods. A phenome scan was performed with UCLEB Consortium data. Allele-specific protein binding was studied using electrophoretic mobility shift assays. Dual-reporter luciferase assays were used to assess the impact of genetic variation on expression. Expression quantitative trait analysis was performed with Advanced Study of Aortic Pathology (ASAP) and Genotype-Tissue Expression (GTEx) consortium data. Results. A suggestive association between QT interval and the locus was observed (rs9982601  p = 0.04). One variant at the locus, rs28451064, showed allele-specific protein binding and its minor allele showed 12% higher luciferase expression (p = 4.82 × 10(-3)) compared to the common allele. The minor allele of rs9982601 was associated with higher expression of the closest upstream genes (SLC5A3 1.30-fold increase p = 3.98 × 10(-5); MRPS6 1.15-fold increase p = 9.60 × 10(-4)) in aortic intima media in ASAP. Both rs9982601 and rs28451064 showed a suggestive association with MRPS6 expression in relevant tissues in the GTEx data. Conclusions. A candidate functional variant, rs28451064, was identified. Future work should focus on identifying the pathway(s) involved.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.language.isoenen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectChromosomes, Human, Pair 21en
dc.subjectHumansen
dc.subjectLong QT Syndromeen
dc.subjectCoronary Diseaseen
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectGenetic Locien
dc.subjectHep G2 Cellsen
dc.titleFunctional Analysis of the Coronary Heart Disease Risk Locus on Chromosome 21q22.en
dc.typeArticle
prism.publicationDate2017en
prism.publicationNameDisease markersen
prism.startingPage1096916
prism.volume2017en
dc.identifier.doi10.17863/CAM.10801
dcterms.dateAccepted2016-12-13en
rioxxterms.versionofrecord10.1155/2017/1096916en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-01en
dc.contributor.orcidBeaney, Katherine E [0000-0001-7544-2055]
dc.contributor.orcidFolkersen, Lasse [0000-0003-0708-9530]
dc.contributor.orcidJefferis, Barbara J [0000-0002-0850-3177]
dc.contributor.orcidWhincup, Peter [0000-0002-5589-4107]
dc.contributor.orcidGaunt, Tom R [0000-0003-0924-3247]
dc.contributor.orcidBen-Shlomo, Yoav [0000-0001-6648-3007]
dc.contributor.orcidKumari, Meena [0000-0001-9716-1035]
dc.contributor.orcidWong, Andrew [0000-0003-2079-4779]
dc.contributor.orcidOng, Kenneth [0000-0003-4689-7530]
dc.contributor.orcidHardy, Rebecca [0000-0001-9949-0799]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidKivimaki, Mika [0000-0002-4699-5627]
dc.contributor.orcidEriksson, Per [0000-0002-5635-2692]
dc.contributor.orcidHumphries, Steve E [0000-0002-8221-6547]
dc.identifier.eissn1875-8630
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/2)
rioxxterms.freetoread.startdate2018-08-24


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

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