Global and regional DNA methylation patterns in heart failure: a case-control analysis

Area of Science:

• Epigenetics
• Cardiovascular Disease Research
• Genomics

Background:

• Heart failure (HF) is a complex syndrome with unclear links to DNA methylation (DNAm) and epigenetic aging.
• Understanding these epigenetic changes is crucial for identifying HF phenotypes and progression.

Purpose of the Study:

• To investigate global and regional DNAm patterns in individuals with and without HF.
• To assess epigenetic aging using methylation clocks (GrimAge and Hannum) in relation to HF.
• To determine the association of DNAm patterns and epigenetic age with HF severity and mortality.

Main Methods:

• Analysis of DNAm using the Illumina MethylationEPIC assay in 2155 individuals from the MyoVasc and Gutenberg Health Studies.
• Calculation of epigenetic age using GrimAge and Hannum methylation clocks.
• Statistical analysis of global and regional DNAm patterns, including CpG sites, shores, and islands.

Main Results:

• HF was associated with an average increase of 19 years in epigenetic age.
• A global decrease in methylation was observed in HF patients (OR: 1.33).
• Epigenetic clocks strongly predicted HF worsening and mortality; methylation differences were most pronounced in genomic shores.

Conclusions:

• Accelerated aging and distinct DNAm patterns are key features of HF, influencing its presence, severity, and consequences.
• HF-related methylation patterns vary across chromosomes and genomic regions.
• CpG islands show a weaker association with HF status but may have a regulatory role.