Epigenetic patterns in blood associated with lipid traits predict incident coronary heart disease events and are enriched for results from genome-wide association studies

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. , Sundstrom, Johan, Krauss, Ronald M. , Arnett, Donna K., Deary, Ian J. , Lind, Lars, Levy, Daniel and Ingelsson, Erik (2017) Epigenetic patterns in blood associated with lipid traits predict incident coronary heart disease events and are enriched for results from genome-wide association studies. Circulation: Cardiovascular Genetics, 10 1: . doi:10.1161/CIRCGENETICS.116.001487


Author 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.
Sundstrom, Johan
Krauss, Ronald M.
Arnett, Donna K.
Deary, Ian J.
Lind, Lars
Levy, Daniel
Ingelsson, Erik
Title Epigenetic patterns in blood associated with lipid traits predict incident coronary heart disease events and are enriched for results from genome-wide association studies
Journal name Circulation: Cardiovascular Genetics   Check publisher's open access policy
ISSN 1942-3268
1942-325X
Publication date 2017-02-17
Sub-type Article (original research)
DOI 10.1161/CIRCGENETICS.116.001487
Open Access Status DOI
Volume 10
Issue 1
Total pages 47
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Collection year 2018
Language eng
Formatted abstract
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 triglycerides and 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 (PTC=0.004, PHDL-C=0.008 and Ptriglycerides=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.
Keyword Cardiovascular diseases
DNA Methylation
Epigenomics
Gene expression
Lipids
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 07 Mar 2017, 00:20:21 EST by System User on behalf of Learning and Research Services (UQ Library)