DNA methylation-based biomarkers for cardiometabolic-related traits and their importance for risk stratification

Area of Science:

• Genomics and Epigenetics
• Cardiovascular and Metabolic Diseases
• Biomarker Discovery

Background:

• Cardiometabolic syndrome prevalence is rising globally, necessitating improved diagnostic and classification tools.
• Existing risk scores and criteria for cardiometabolic syndrome lack universal acceptance.
• Novel molecular biomarkers are crucial for understanding cardiometabolic syndrome risk, onset, and progression.

Purpose of the Study:

• To provide an overview of second-generation DNA methylation (DNAm)-based cardiometabolic biomarkers.
• To discuss methodological advancements in DNAm biomarker development.
• To highlight the implications for interpretation and generalizability of findings.

Main Methods:

• Development of second-generation DNAm-based biomarkers using whole blood DNA methylation levels.
• Identification of key CpG sites through two-step machine learning procedures.
• Linear combination of individual DNAm levels to create predictive biomarkers.

Main Results:

• Consistent associations between DNAm levels at specific CpG sites and cardiometabolic conditions.
• Creation of DNAm-based biomarkers applicable even retrospectively.
• Demonstration of DNAm biomarkers' utility in populations without observed cardiometabolic phenotypes.

Conclusions:

• Second-generation DNAm biomarkers offer a novel approach to cardiometabolic syndrome classification.
• These biomarkers enhance risk stratification beyond traditional factors.
• Future research should address limitations and explore further applications of DNAm biomarkers.