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

Abstract

Recent findings The prevalence of cardiometabolic syndrome in adults is increasing worldwide, highlighting the importance of biomarkers for individuals’ classification based on their health status. Although cardiometabolic risk scores and diagnostic criteria have been developed aggregating health effects of individual conditions on the overall syndrome, none of them has gained unanimous acceptance. Therefore, novel molecular biomarkers have been developed to better understand the risk, onset and progression of both individual conditions and the overall cardiometabolic syndrome. Summary Consistent associations between whole blood DNA methylation (DNAm) levels at several single genomic (i.e. CpG) sites and both individual and aggregated cardiometabolic conditions supported the creation of second-generation DNAm-based cardiometabolic-related biomarkers. These biomarkers linearly combine individual DNAm levels from key CpG sites, selected by two-step machine learning procedures. They can be used, even retrospectively, in populations with extant whole blood DNAm levels and without observed cardiometabolic phenotypes. Purpose of review Here, we offer an overview of the second-generation DNAm-based cardiometabolic biomarkers, discussing methodological advancements and implications on the interpretation and generalizability of the findings. We finally emphasize the contribution of DNAm-based biomarkers for risk stratification beyond traditional factors and discuss limitations and future directions of the field.