Association Between Mortality and Heritability of the Scale of Aging Vigor in Epidemiology

Objectives To investigate the association between mortality and heritability of a rescaled Fried frailty index, the Scale of Aging Vigor in Epidemiology (SAVE), to determine its value for genetic analyses. Design Longitudinal, community‐based cohort study. Setting The Long Life Family Study (LLFS) in the United States and Denmark. Participants Long‐lived individuals (N = 4,875, including 4,075 genetically related individuals) and their families (N = 551). Measurements The SAVE was administered to 3,599 participants and included weight change, weakness (grip strength), fatigue (questionnaire), physical activity (days walked in prior 2 weeks), and slowness (gait speed); each component was scored 0, 1, or 2 using approximate tertiles, and summed (range 0 (vigorous) to 10 (frail)). Heritability was determined using a variance component–based family analysis using a polygenic model. Association with mortality in the proband generation (N = 1,421) was calculated using Cox proportional hazards mixed‐effect models. Results Heritability of the SAVE was 0.23 (P < .001) overall (n = 3,599), 0.31 (P < .001) in probands (n = 1,479), and 0.26 (P < .001) in offspring (n = 2,120). In adjusted models, higher SAVE scores were associated with higher mortality (score 5–6: hazard ratio (HR) = 2.83, 95% confidence interval (CI) = 1.46–5.51; score 7–10: HR = 3.40, 95% CI = 1.72–6.71) than lower scores (0–2). Conclusion The SAVE was associated with mortality and was moderately heritable in the LLFS, suggesting a genetic component to age‐related vigor and frailty and supporting its use for further genetic analyses.