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dc.contributor.authorVarga, Tibor Ven
dc.contributor.authorKurbasic, Azraen
dc.contributor.authorAine, Mattiasen
dc.contributor.authorEriksson, Pontusen
dc.contributor.authorAli, Ashfaqen
dc.contributor.authorHindy, Georgeen
dc.contributor.authorGustafsson, Stefanen
dc.contributor.authorLuan, Jian'anen
dc.contributor.authorShungin, Dmitryen
dc.contributor.authorChen, Yanen
dc.contributor.authorSchulz, Christina-Alexandraen
dc.contributor.authorNilsson, Peter Men
dc.contributor.authorHallmans, Göranen
dc.contributor.authorBarroso, Inesen
dc.contributor.authorDeloukas, Panosen
dc.contributor.authorLangenberg, Claudiaen
dc.contributor.authorScott, Robert Aen
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorLind, Larsen
dc.contributor.authorIngelsson, Eriken
dc.contributor.authorMelander, Olleen
dc.contributor.authorOrho-Melander, Marjuen
dc.contributor.authorRenström, Fridaen
dc.contributor.authorFranks, Paul Wen
dc.date.accessioned2017-08-15T13:03:13Z
dc.date.available2017-08-15T13:03:13Z
dc.date.issued2017-08en
dc.identifier.issn0300-5771
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/266412
dc.description.abstractBACKGROUND: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids. METHODS: Participants from the GLACIER Study (Nmax = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms; replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (ΔTC) and triglycerides (ΔTG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; Nmax = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N ∼ 190 000) and functional annotation for the top ranking variants. RESULTS: In total, 956 variants were associated (P < 0.01) with either ΔTC or ΔTG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with ΔTG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 × 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 × 10(-6)). The rs7412 variant at APOE was associated with ΔTC in GLACIER (P < 1.7 × 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with ΔTC and for ΔTG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 × 10(-4)), multiple variants at HPR (Pmin = 1.5 × 10(-6)) and a variant at SIX5 (P = 1.9 × 10(-4)) showed evidence for association with CAD. CONCLUSIONS: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.
dc.format.mediumPrinten
dc.languageengen
dc.language.isoenen
dc.subjectHumansen
dc.subjectLipidsen
dc.subjectProspective Studiesen
dc.subjectCross-Sectional Studiesen
dc.subjectGenotypeen
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectAdulten
dc.subjectAgeden
dc.subjectMiddle Ageden
dc.subjectEuropean Continental Ancestry Groupen
dc.subjectSwedenen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectCoronary Artery Diseaseen
dc.subjectMeta-Analysis as Topicen
dc.subjectGenome-Wide Association Studyen
dc.subjectGenetic Locien
dc.titleNovel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults.en
dc.typeArticle
prism.endingPage1222
prism.issueIdentifier4en
prism.publicationDate2017en
prism.publicationNameInternational journal of epidemiologyen
prism.startingPage1211
prism.volume46en
dc.identifier.doi10.17863/CAM.10726
dcterms.dateAccepted2016-08-04en
rioxxterms.versionofrecord10.1093/ije/dyw245en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-08en
dc.contributor.orcidVarga, Tibor V [0000-0002-2383-699X]
dc.contributor.orcidAine, Mattias [0000-0002-0851-5952]
dc.contributor.orcidHindy, George [0000-0002-7257-9299]
dc.contributor.orcidLuan, Jian'an [0000-0003-3137-6337]
dc.contributor.orcidBarroso, Ines [0000-0001-5800-4520]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidOrho-Melander, Marju [0000-0002-3578-2503]
dc.contributor.orcidFranks, Paul W [0000-0002-0520-7604]
dc.identifier.eissn1464-3685
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idMRC (MC_PC_13046)
pubs.funder-project-idMedical Research Council (5PV0E)
pubs.funder-project-idMRC (MC_PC_13048)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
pubs.funder-project-idMedical Research Council (G0701863)
pubs.funder-project-idMedical Research Council (MC_U106179471)
rioxxterms.freetoread.startdate2018-08-25


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