Details

Autor(en) / Beteiligte

• Hedman, Åsa K
• Mendelson, Michael M
• Marioni, Riccardo E
• Gustafsson, Stefan
• Joehanes, Roby
• Irvin, Marguerite R
• Zhi, Degui
• Sandling, Johanna K
• Yao, Chen
• Liu, Chunyu
• Liang, Liming
• Huan, Tianxiao
• McRae, Allan F
• Demissie, Serkalem
• Shah, Sonia
• Starr, John M
• Cupples, L Adrienne
• Deloukas, Panos
• Spector, Timothy D
• Sundström, Johan
• Krauss, Ronald M
• Arnett, Donna K
• Deary, Ian J
• Lind, Lars
• Levy, Daniel
• Ingelsson, Erik

Titel

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

Ist Teil von

• Circulation. Cardiovascular genetics, 2017, Vol.10 (1)

Ort / Verlag

United States

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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 ( <1.08E-07) and replicated 33 (at Bonferroni-corrected <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 triglycerides and high-density lipoprotein cholesterol (HDL-C; cg27243685; =8.1E-26 and 9.3E-19) was associated with -expression of a reverse cholesterol transporter ( =7.2E-28) and incident cardiovascular disease events (hazard ratio per SD increment, 1.38; 95% confidence interval, 1.15-1.66; =0.0007). We found significant -methylation quantitative trait loci at 64% of the 193 CpGs with an enrichment of signals from genome-wide association studies of lipid levels ( =0.004, =0.008 and =0.00003) and coronary heart disease ( =0.0007). For example, genome-wide significant variants associated with low-density lipoprotein cholesterol and coronary heart disease at were -methylation quantitative trait loci for a low-density lipoprotein cholesterol-related differentially methylated locus. 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.