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



Longitudinal, community-based cohort study.



The Long Life Family Study (LLFS) in the United States and Denmark.



Long-lived individuals (N = 4,875, including 4,075 genetically related individuals) and their families (N = 551).



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.



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).



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.
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Jason L
JL
Sanders
Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
Jatinder
J
Singh
Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
Ryan L
RL
Minster
Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Jeremy D
JD
Walston
Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Amy M
AM
Matteini
Department of Epidemiology, Biostatistics and Biodemography, University of Southern Denmark, Odense, Denmark.
Kaare
K
Christensen
Department of Neurology, Columbia University, New York, New York.
Richard
R
Mayeux
Division of Statistical Genetics, Washington University in St. Louis, St. Louis, Missouri.
Ingrid B
IB
Borecki
Department of Medicine, Boston University, Boston, Massachusetts.
Thomas
T
Perls
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Anne B
AB
Newman
D000369:Aged, 80 and over; D001835:Body Weight / Q000235:genetics; D015331:Cohort Studies; D003431:Cross-Cultural Comparison; D003718:Denmark; D004185:Disability Evaluation; D015444:Exercise; D005260:Female; D016330:Frail Elderly / Q000706:statistics & numerical data*; D005684:Gait / Q000235:genetics; D005838:Genotype; D018737:Hand Strength; D006304:Health Status; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics; D010809:Physical Fitness; D013223:Statistics as Topic; D014481:United States
epidemiology; frailty; genetics; longevity; phenotype