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dc.contributor.authorCannon ME
dc.contributor.authorDuan Q
dc.contributor.authorWu Y
dc.contributor.authorZeynalzadeh M
dc.contributor.authorXu Z
dc.contributor.authorKangas AJ
dc.contributor.authorSoininen P
dc.contributor.authorAla-Korpela M
dc.contributor.authorCivelek M
dc.contributor.authorLusis AJ
dc.contributor.authorKuusisto J
dc.contributor.authorCollins FS
dc.contributor.authorBoehnke M
dc.contributor.authorTang H
dc.contributor.authorLaakso M
dc.contributor.authorLi Y
dc.contributor.authorMohlke K
dc.date.accessioned2018-01-08T14:16:39Z
dc.date.available2018-01-08T14:16:39Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/5137
dc.description.abstractRecent genome-wide association studies (GWAS) have identified variants associated with high-density lipoprotein cholesterol (HDL-C) located in or near the ANGPTL8 gene. Given the extensive sharing of GWAS loci across populations, we hypothesized that at least one shared variant at this locus affects HDL-C. The HDL-C–associated variants are coincident with expression quantitative trait loci for ANGPTL8 and DOCK6 in subcutaneous adipose tissue; however, only ANGPTL8 expression levels are associated with HDL-C levels. We identified a 400-bp promoter region of ANGPTL8 and enhancer regions within 5 kb that contribute to regulating expression in liver and adipose. To identify variants functionally responsible for the HDL-C association, we performed fine-mapping analyses and selected 13 candidate variants that overlap putative regulatory regions to test for allelic differences in regulatory function. Of these variants, rs12463177-G increased transcriptional activity (1.5-fold, P = 0.004) and showed differential protein binding. Six additional variants (rs17699089, rs200788077, rs56322906, rs3760782, rs737337, and rs3745683) showed evidence of allelic differences in transcriptional activity and/or protein binding. Taken together, these data suggest a regulatory mechanism at the ANGPTL8 HDL-C GWAS locus involving tissue-selective expression and at least one functional variant.en
dc.language.isoENen
dc.publisherGenetics Society of Americaen
dc.relation.ispartofseriesG3: Genes, genomes, Geneticsen
dc.relation.urihttp://dx.doi.org/10.1534/g3.117.300088en
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/en
dc.subjectGeneticsen
dc.subjectGene Expressionen
dc.subjectCholesterolen
dc.subjectTranscriptionen
dc.subjectComplex genetic traitsen
dc.titleTrans-ancestry Fine Mapping and Molecular Assays Identify Regulatory Variants at the ANGPTL8 HDL-C GWAS Locusen
dc.description.versionpublished versionen
dc.contributor.departmentSchool of Pharmacy, Activitiesen
dc.contributor.departmentSchool of Medicine / Clinical Medicineen
uef.solecris.id49362813en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7-HEALTH/201681/EU/NOVEL PREP1-DEPENDENT TRANSCRIPTIONAL NETWORKS IN THE CONTROL OF INSULIN SENSITIVITY/PREPOBEDIAen
dc.relation.doi10.1534/g3.117.300088en
dc.description.reviewstatuspeerRevieweden
dc.relation.issn2160-1836en
dc.relation.volume[Epub ahead of print July 28, 2017]en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
uef.solecris.openaccessOpen access -julkaisukanavassa ilmestynyt julkaisu


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