Associations Between PEGS, Cardiometabolic Factors, and Demographics in US Adults

To better understand the potential benefit of using poly-epigenetic scores (PEGS) for cardiometabolic risk factors based on demographics and health behaviors in older US adults, researchers used results from established epigenome-wide association studies to develop PEGS from whole-blood DNA methylation for systolic and diastolic blood pressure, body mass index, C-reactive protein, and high- and low-density lipoprotein cholesterol, triglycerides, and fasting glucose. Demographics included age, sex, and educational attainment; health behaviors included smoking, alcohol consumption, and physical activity.

Results were published in Epigenetics.

Researchers used data from the Health and Retirement Study, a representative longitudinal cohort of over 20,000 adults older than 50. The researchers focused on survey participants aged 55 or older with available DNA methylation and, using sample weights, included 3,855 participants in their analyses. The mean age of participants was 69.5 years. Cardiometabolic risk factor and PEGS correlations were evaluated using Pearson correlation; linear regression was used to investigate the association between each PEGS and its corresponding cardiometabolic risk factor.

The researchers found that all PEGS were positively associated with the respective cardiometabolic traits (P>0.05), which is considered significant according to the researchers. All associations remained similar after adjustment for health behaviors. Differences in race/ethnicity were nonsignificant.

Of note, younger participants had greater PEGS associations for body mass index, high-density lipoprotein cholesterol, and triglycerides. Body mass index and high-density lipoprotein cholesterol associations were greater in women. Compared with those without a high school degree, participants with a high school degree had a stronger association with C-reactive protein. A higher association was also seen for high-density lipoprotein cholesterol in current smokers versus current nonsmokers.

“In summary, we found strong and positive associations between all PEGSs and their corresponding cardiometabolic risk factors in US older adults, with most associations stable across racial/ethnic groups…The results contribute to the growing body of literature on utilizing whole-genome DNA methylation data in the context of precision health,” the researchers concluded.

Reference

Lin L, Zhao W, Li Z, et al. Poly-epigenetic scores for cardiometabolic risk factors interact with demographic factors and health behaviors in older US adults. Epigenetics. 2025;20(1):2469205. Published online February 20, 2025. doi:10.1080/15592294.2025.2469205