Associations Between DNA Methylation Age Acceleration, Depressive Symptoms, and Cardiometabolic Traits in African American Mothers From the InterGEN Study

BACKGROUND: African American women (AAW) have a high risk of both cardiometabolic (CM) illness and depressive symptoms. Depressive symptoms co-occur in individuals with CM illness at higher rates than the general population, and accelerated aging may explain this. In this secondary analysis, we examined associations between age acceleration; depressive symptoms; and CM traits (hypertension. diabetes mellitus [DM], and obesity) in a cohort of AAW. METHODS: Genomic and clinical data from the InterGEN cohort (n =227) were used. Age acceleration was based on the Horvath method of DNA methylation (DNAm) age estimation. Accordingly, DNAm age acceleration (DNAm AA) was defined as the residuals from a linear regression of DNAm age on chronological age. Spearman's correlations. linear and logistic regression examined associations between DNAm AA, depressive symptoms. and CM traits. RESULTS: DNAm AA did not associate with total depressive symptom scores. DNAm AA correlated with specific symptoms including self-disgust/self-hate (-0.13.95% CI -0.26. -0.01); difficulty with making decisions (-0.15.95% CI -0.28, -0.02): and worry over physical health (0.15, 95% CI 0.02. 0.28). but were not statistically significant after multiple comparison correction. DNAm AA associated with obesity (0.08. 95% CI 1.02, 1.16), hypertension (0.08. 95% CI 1.01. 1.17). and DM (0.20. 95% CI 1.09. 1.40). after adjustment for potential confounders. CONCLUSIONS: Associations between age acceleration and depressive symptoms may be highly nuanced and dependent on study design contexts. Factors other than age acceleration may explain the connection between depressive symptoms and CM traits. AAW with CM traits may be at increased risk of accelerated aging.