Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies [Elektronisk resurs]
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Hedman, Åsa K. (författare)
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Mendelson, Michael M. (författare)
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Marioni, Riccardo E. (författare)
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Gustafsson, Stefan (författare)
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Joehanes, Roby (författare)
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Irvin, Marguerite R. (författare)
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Zhi, Degui (författare)
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Sandling, Johanna K. (författare)
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Yao, Chen (författare)
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Liu, Chunyu (författare)
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Liang, Liming (författare)
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Huan, Tianxiao (författare)
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McRae, Allan F. (författare)
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Demissie, Serkalem (författare)
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Shah, Sonia (författare)
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Starr, John M. (författare)
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Cupples, L. Adrienne (författare)
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Deloukas, Panos (författare)
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Spector, Timothy D. (författare)
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Sundström, Johan (författare)
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Krauss, Ronald M. (författare)
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Arnett, Donna K. (författare)
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Deary, Ian J. (författare)
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Lind, Lars (författare)
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Levy, Daniel (författare)
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Ingelsson, Erik 1975- (författare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
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Uppsala universitet Science for Life Laboratory, SciLifeLab (utgivare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
- LIPPINCOTT WILLIAMS & WILKINS 2017
- Engelska.
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Ingår i: Circulation. - 1942-325X. ; 10:1
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Sammanfattning
Ämnesord
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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.
Ämnesord
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Cardiac and Cardiovascular Systems (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Kardiologi (hsv)
- Basic Medicine (hsv)
- Medical Genetics (hsv)
- Medicinska grundvetenskaper (hsv)
- Medicinsk genetik (hsv)
Indexterm och SAB-rubrik
- cardiovascular diseases
- DNA Methylation
- epigenomics
- gene expression
- lipids
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