Association of DNA methylation-predicted GDF15 and frailty in older adults based on NHANES 1999–2002

GDF15 (growth differentiation factor 15) serves as a significant indicator across diverse physiological states and disease processes. Increased GDF15 concentrations are strongly implicated in heightened frailty risk. Nevertheless, the prognostic utility of DNA methylation (DNAm)-estimated GDF15 levels for frailty remains inadequately investigated. This research seeks to examine the association between DNAm-predicted GDF15 concentrations and frailty among older individuals residing in the United States. This investigation leveraged data from the 1999 to 2002 National Health and Nutrition Examination Survey, employing a cross-sectional design. This study included 1553 community-dwelling older adults. Weighted logistic regression was utilized, supplemented by sensitivity assessments, to evaluate the link between DNAm-predicted GDF15 concentrations and frailty in participants aged ≥60 years. The restricted cubic spline technique was applied to further characterize this association. Additionally, covariate-specific subgroup evaluations and interaction assessments were visualized using a forest plot. Elevated concentrations of GDF15 predicted by DNA methylation were statistically associated with greater frailty likelihood (odds ratio = 1.14, 95% confidence interval: 1.03-1.26). Individuals within the highest third tertile of DNAm-predicted GDF15 exhibited a significantly increased frailty risk (odds ratio = 1.46, 95% confidence interval: 1.01-2.13). Restricted cubic splines analysis revealed a linear dose-response association between DNAm-estimated GDF15 concentrations and frailty. This positive link was persistently evident across diverse subgroups. This cross-sectional study demonstrates a positive correlation linking DNAm-predicted GDF15 concentrations to frailty.