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Sökning: onr:"swepub:oai:DiVA.org:uu-320506" > Epigenetic Patterns...

  • Hedman, Åsa K.Karolinska Institutet,Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden. (författare)

Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • LIPPINCOTT WILLIAMS & WILKINS,2017
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-320506
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-320506URI
  • https://doi.org/10.1161/CIRCGENETICS.116.001487DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135397784URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Background- Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. Methods and Results- To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals. We identified 193 CpGs associated with lipid levels in the discovery stage (P < 1.08E-07) and replicated 33 (at Bonferroni-corrected P < 0.05), including 25 novel CpGs not previously associated with lipids. Genes at lipid-associated CpGs were enriched in lipid and amino acid metabolism processes. A differentially methylated locus associated with triglyceridesand high-density lipoprotein cholesterol (HDL- C; cg27243685; P= 8.1E-26 and 9.3E-19) was associated with cis-expression of a reverse cholesterol transporter (ABCG1; P= 7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; P= 0.0007). We found significant cis-methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels (P-TC = 0.004, PHDL-C = 0.008 and P-triglycerides = 0.00003) and coronary heart disease ( P= 0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at APOB were cis-methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. Conclusions-We report novel associations of DNA methylation with lipid levels, describe epigenetic mechanisms related to previous genome-wide association studies discoveries, and provide evidence implicating epigenetic regulation of reverse cholesterol transport in blood in relation to occurrence of cardiovascular disease events.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Mendelson, Michael M.Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Boston, MA 02215 USA.;Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.,Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland.,Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. (författare)
  • Marioni, Riccardo E.Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. (författare)
  • Gustafsson, StefanUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)stegu732 (författare)
  • Joehanes, RobyFramingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.;Harvard Med Sch, Hebrew Senior Life, Boston, MA USA. (författare)
  • Irvin, Marguerite R.Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. (författare)
  • Zhi, DeguiUniv Alabama Birmingham, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA. (författare)
  • Sandling, Johanna K.Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab(Swepub:uu)josan062 (författare)
  • Yao, ChenFramingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. (författare)
  • Liu, ChunyuFramingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Dept Biosci, Boston, MA 02215 USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. (författare)
  • Liang, LimingHarvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.,Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Dept Biosci, Boston, MA 02215 USA. (författare)
  • Huan, TianxiaoFramingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. (författare)
  • McRae, Allan F.Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. (författare)
  • Demissie, SerkalemFramingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Dept Biosci, Boston, MA 02215 USA. (författare)
  • Shah, SoniaUniv Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. (författare)
  • Starr, John M.Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland. (författare)
  • Lind, LarsUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (författare)
  • Deloukas, PanosQueen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia. (författare)
  • Spector, Timothy D.Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. (författare)
  • Sundström, JohanUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)johasund (författare)
  • Krauss, Ronald M.Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. (författare)
  • Arnett, Donna K.Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA. (författare)
  • Deary, Ian J.Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland. (författare)
  • Lind, LarsUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (författare)
  • Levy, DanielFramingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. (författare)
  • Ingelsson, Erik,1975-Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr,Mail Code 5773, Stanford, CA 94305 USA.(Swepub:uu)ering425 (författare)
  • Uppsala universitetMolekylär epidemiologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Circulation: LIPPINCOTT WILLIAMS & WILKINS10:11942-325X1942-3268

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