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Epigenetic Patterns...
Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies
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- Hedman, Åsa K. (author)
- Karolinska Institutet,Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
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- Mendelson, Michael M. (author)
- 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.
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- Marioni, Riccardo E. (author)
- 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.
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- Gustafsson, Stefan (author)
- Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab
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- Joehanes, Roby (author)
- Framingham 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.
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- Irvin, Marguerite R. (author)
- Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
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- Zhi, Degui (author)
- Univ Alabama Birmingham, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA.
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- Sandling, Johanna K. (author)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Yao, Chen (author)
- Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
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- Liu, Chunyu (author)
- Framingham 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.
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- Liang, Liming (author)
- Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.,Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Dept Biosci, Boston, MA 02215 USA.
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- Huan, Tianxiao (author)
- Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
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- McRae, Allan F. (author)
- Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
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- Demissie, Serkalem (author)
- Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Dept Biosci, Boston, MA 02215 USA.
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- Shah, Sonia (author)
- Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
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- Starr, John M. (author)
- Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland.
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- Lind, Lars (author)
- Uppsala universitet,Kardiovaskulär epidemiologi
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- Deloukas, Panos (author)
- Queen 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.
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- Spector, Timothy D. (author)
- Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
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- Sundström, Johan (author)
- Uppsala universitet,Kardiovaskulär epidemiologi
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- Krauss, Ronald M. (author)
- Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
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- Arnett, Donna K. (author)
- Univ Kentucky, Coll Publ Hlth, Lexington, KY 40506 USA.
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- Deary, Ian J. (author)
- Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland.
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- Lind, Lars (author)
- Uppsala universitet,Kardiovaskulär epidemiologi
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- Levy, Daniel (author)
- Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
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- Ingelsson, Erik, 1975- (author)
- 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.
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(creator_code:org_t)
- LIPPINCOTT WILLIAMS & WILKINS, 2017
- 2017
- English.
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:1
- Related links:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- cardiovascular diseases
- DNA Methylation
- epigenomics
- gene expression
- lipids
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hedman, Åsa K.
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Mendelson, Micha ...
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Marioni, Riccard ...
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Gustafsson, Stef ...
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Joehanes, Roby
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Irvin, Marguerit ...
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show more...
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Zhi, Degui
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Sandling, Johann ...
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Yao, Chen
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Liu, Chunyu
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Liang, Liming
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Huan, Tianxiao
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McRae, Allan F.
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Demissie, Serkal ...
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Shah, Sonia
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Starr, John M.
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Lind, Lars
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Deloukas, Panos
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Spector, Timothy ...
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Sundström, Johan
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Krauss, Ronald M ...
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Arnett, Donna K.
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Deary, Ian J.
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Levy, Daniel
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Ingelsson, Erik, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Circulation
- By the university
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Uppsala University
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Karolinska Institutet