Temporal associations between leukocytes DNA methylation and blood lipids: a longitudinal study

Area of Science:

• Epigenetics
• Genomics
• Metabolic Health

Background:

• Epigenome-wide association studies (EWAS) on blood lipids and DNA methylation primarily focus on European ancestry.
• Limited longitudinal data exists to establish causal relationships between DNA methylation and lipid measures.

Purpose of the Study:

• To investigate associations between DNA methylation and lipid profiles in a Chinese population.
• To explore the temporal sequence of these associations using longitudinal data.
• To examine mediation effects of DNA methylation on the relationship between BMI and lipids.

Main Methods:

• Utilized Illumina 450K/EPIC arrays for DNA methylation analysis in two Chinese cohorts (n=1084 and n=988).
• Employed cross-lagged and mediation analyses on longitudinal data.
• Focused on peripheral blood leukocytes DNA methylation and four lipid measures.

Main Results:

• Identified 23 associations between 19 CpG sites and lipid measures, including 4 novel CpG sites near TMEM49, SNX5/SNORD17, and CCDC7 genes.
• Found temporal associations between DNA methylation at 2 CpG sites and triglyceride levels, and 2 CpG sites and high-density lipoprotein-cholesterol (HDL-C) levels.
• Demonstrated partial mediation of the body mass index-HDL-C association by cg06500161 (ABCG1) methylation (10.1% mediation).

Conclusions:

• DNA methylation levels of ABCG1, AKAP1, and SREBF1 are implicated in lipid metabolism.
• Provides longitudinal evidence supporting the role of specific DNA methylation sites in lipid homeostasis regulation.
• Highlights potential epigenetic mechanisms linking metabolic factors to lipid profiles.