Background: Metabolic syndrome (MetS), which is characterised by abnormalities of fasting glucose, triglycerides, HDL cholesterol, blood pressure and waist circumference, increases the risk of cardiovascular disease and all-cause mortality. While numerous studies have examined the relationship between DNA methylation and its components using methylation arrays in relatively younger populations, there is limited research focusing on more comprehensive DNA methylation assays and examining older adults. Here, we aimed to identify blood DNA methylation sites associated with MetS and its components based on DNA methylation sequencing data in older adults.
Methods: MethylC-capture sequencing was performed on blood DNA extracted from 260 unrelated individuals (aged 65-89 yrs, mean age=74.85 SD 6.1) from the Sydney Memory and Ageing Study and the Older Australian Twins Study. MetS was defined as per the harmonized National Cholesterol Education Program (Alberti et al, Circulation, 2009, 120:16). Epigenome-wide association studies (EWAS) were performed using linear regression to identify methylated sites associated with MetS and its components, adjusting for covariates.
Results: After quality control, there were 4528775 methylation sites available for analysis. There were 18 and 10 EWAS significant (p≤3.6x10-8) loci associated with glucose and triglycerides, respectively. No significant loci were found for MetS or its other components. Out of the 15 sites associated with glucose near protein-coding genes (n=15), methylation in/near four of these genes, PDE4DIP, JARID2, CMIP and NUP214, has been previously reported with glucose levels.
Conclusion: We identified putative methylated sites associated with components of the metabolic syndrome in older cohorts for replication studies and functional investigation.