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Epigenome-wide association study (EWAS) on lipids: the Rotterdam Study
Kim V E Braun1, Klodian Dhana1, Paul S de Vries1,2
1Department of Epidemiology, Erasmus University Medical Center, Dr. Molewaterplein 50, Office NA2906, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Clinical Epigenetics
|February 15, 2017
Summary
This study links DNA methylation patterns to blood lipid levels, identifying specific CpG sites associated with triglycerides and HDL cholesterol. These findings offer insights into the epigenetic regulation of lipid metabolism.
Area of Science:
- Epigenetics
- Molecular Biology
- Human Genetics
Background:
- DNA methylation is a crucial epigenetic mechanism.
- Epigenetic modifications are increasingly recognized for their role in metabolic regulation.
- Previous research suggests a link between DNA methylation and blood lipid profiles.
Purpose of the Study:
- To identify specific CpG sites where DNA methylation levels correlate with blood lipid concentrations (triglycerides, HDL-C, LDL-C, total cholesterol).
- To validate these associations in an independent cohort.
- To elucidate epigenetic mechanisms influencing lipid metabolism.
Main Methods:
- Genome-wide DNA methylation was assessed using the Illumina Methylation 450 array in whole blood.
- Linear mixed-effect models were employed to analyze associations between methylation beta values and lipid levels.
- Statistical significance was determined using a Bonferroni-corrected p-value threshold of 1.08 × 10-7, with adjustments for covariates.
Main Results:
- Five CpG sites, annotated to genes including DHCR24, CPT1A, ABCG1, and SREBF1, were identified and successfully replicated.
- Four CpG sites showed significant associations with triglyceride levels, linked to CPT1A, ABCG1, and SREBF1.
- Two CpG sites were associated with HDL-C levels, specifically near DHCR24 and within ABCG1.
Conclusions:
- An association was confirmed between HDL-C levels and methylation of a CpG site near DHCR24, a gene involved in cholesterol biosynthesis.
- Previously reported associations between lipid levels and methylation of CpG sites in CPT1A, ABCG1, and SREBF1 were validated.
- The findings contribute to understanding the epigenetic underpinnings of lipid metabolism.
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