Multi-ancestry epigenome-wide analyses identify methylated sites associated with aortic augmentation index in TOPMed...

Area of Science:

• Cardiovascular Epigenetics
• Genomics and Precision Medicine
• Atherosclerosis Research

Background:

• Arterial stiffness (AS) and pulsatile hemodynamics (PH) are crucial indicators of cardiovascular risk.
• The epigenetic underpinnings, specifically DNA methylation patterns, contributing to AS/PH are not well understood.
• Identifying these epigenetic links is vital for understanding cardiovascular disease pathophysiology.

Purpose of the Study:

• To investigate the association between DNA methylation and arterial stiffness/pulsatile hemodynamics.
• To identify specific CpG sites and co-methylated regions linked to AS/PH measures.
• To uncover potential epigenetic biomarkers for cardiovascular risk.

Main Methods:

• Epigenome-wide association analysis (EWAS) was performed on multi-ancestry cohorts from TOPMed MESA.
• Eight measures of AS/PH were correlated with CpG sites and co-methylated regions.
• Follow-up analyses included gene set enrichment and expression quantitative trait methylation analyses.

Main Results:

• One genome-wide significant CpG site (cg20711926-CYP1B1) was associated with aortic augmentation index (AIx).
• Three additional CpGs (cg23800023-ETS1, cg08426368-TGFB3, cg17350632-HLA-DPB1) were prioritized for AIx.
• ETS1 and HLA-DPB1 showed significant correlations between whole blood and aorta tissue, suggesting potential biomarker roles.

Conclusions:

• DNA methylation likely plays a role in regulating genes associated with arterial stiffness and pulsatile hemodynamics.
• Specific genes like ETS1 and HLA-DPB1 emerge as potential targets for understanding and potentially regulating AS/PH.
• These findings contribute to the understanding of epigenetic mechanisms in cardiovascular disease.