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  • Varga, Tibor V.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital (author)

Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2016-11-17
  • Oxford University Press (OUP),2017
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-335751
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-335751URI
  • https://doi.org/10.1093/ije/dyw245DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-140479URI
  • https://lup.lub.lu.se/record/1cf44389-a077-45e9-ab0e-2b4da333af5bURI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Background: 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 (N-max = 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 (Delta TC) and triglycerides (Delta TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; N-max = 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 similar to 190 000) and functional annotation for the top ranking variants.Results: In total, 956 variants were associated (P < 0.01) with either Delta TC or Delta TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with Delta TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 x 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 x 10(-6)). The rs7412 variant at APOE was associated with DTC in GLACIER (P < 1.7 x 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with Delta TC and for Delta TG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 x 10(-4)), multiple variants at HPR (P-min = 1.5 x 10(-6)) and a variant at SIX5 (P = 1.9 x 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.

Subject headings and genre

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  • Kurbasic, AzraLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mats-aku (author)
  • Aine, MattiasLund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-mai (author)
  • Eriksson, PontusLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-pte (author)
  • Ali, AshfaqLund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit,Univ Cambridge, Epidemiol Unit, Med Res Council,Skåne University Hospital,University of Cambridge (author)
  • Hindy, GeorgeSkåne Univ Hosp, Diabet & Cardiovasc Dis Genet Epidemiol,Skåne University Hospital(Swepub:lu)med-ghu (author)
  • Gustafsson, StefanUppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi(Swepub:uu)stegu732 (author)
  • Luan, Jian'anUniv Cambridge, Epidemiol Unit, Med Res Council,University of Cambridge (author)
  • Shungin, DmitryUmeå University,Lund University,Lunds universitet,Umeå universitet,Institutionen för odontologi,Lund Univ, Skane Univ Hosp, Malmo, Sweden,Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Odontol;Umeå Univ, Dept Publ Hlth & Clin Med,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-dsn (author)
  • Chen, YanLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-ync (author)
  • Schulz, Christina AlexandraLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-csc (author)
  • Nilsson, Peter M.Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medf-pni (author)
  • Hallmans, Göran,1947-Umeå University,Umeå universitet,Enheten för biobanksforskning,Umeå Univ, Dept Biobank Res(Swepub:umu)goha0001 (author)
  • Barroso, InesWellcome Trust Sanger Inst.;Addenbrookes Hosp, Metab Res Labs, Cambridge, Hosp, Metab Res Labs; Addenbrookes Hosp, NIHR Cambridge BiomeEngland.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr,Wellcome Trust Sanger Institute,Addenbrooke's Hospital (author)
  • Deloukas, PanosBarts & London Queen Marys Sch Med & Dent, William Harvey Res Inst.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah,Queen Mary University,King Abdulaziz University (author)
  • Langenberg, ClaudiaUniv Cambridge, Epidemiol Unit, Med Res Council,University of Cambridge (author)
  • Scott, Robert A.Univ Cambridge, Epidemiol Unit, Med Res Council (author)
  • Wareham, Nicholas J.Univ Cambridge, Epidemiol Unit, Med Res Council,University of Cambridge (author)
  • Lind, LarsUppsala University,Uppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (author)
  • Ingelsson, Erik,1975-Uppsala University,Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford,Wellcome Trust Centre for Human Genetics(Swepub:uu)ering425 (author)
  • Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-ome (author)
  • Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-mor (author)
  • Renström, FridaUmeå University,Lund University,Lunds universitet,Umeå universitet,Enheten för biobanksforskning,Lund Univ, Skane Univ Hosp, Malmo, Sweden,Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Biobank Res,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-frm (author)
  • Franks, Paul W.Umeå University,Lund University,Lunds universitet,Umeå universitet,Medicin,Lund Univ, Skane Univ Hosp, Malmo, Sweden ; Harvard, Boston, MA USA,Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Publ Hlth & Clin Med;Harvard TH Chan Sch Publ Hlth, Dept Nutr,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital,Harvard University(Swepub:lu)med-plf (author)
  • Genetisk och molekylär epidemiologiForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:International Journal of Epidemiology: Oxford University Press (OUP)46:4, s. 1211-12220300-57711464-3685

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