Jason L Sanders1, Jatinder Singh2, Ryan L Minster2, Jeremy D Walston3, Amy M Matteini3, Kaare Christensen4, Richard Mayeux5, Ingrid B Borecki6, Thomas Perls7, Anne B Newman1. 1. Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania. 2. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania. 3. Department of Medicine, Johns Hopkins University, Baltimore, Maryland. 4. Department of Epidemiology, Biostatistics and Biodemography, University of Southern Denmark, Odense, Denmark. 5. Department of Neurology, Columbia University, New York, New York. 6. Division of Statistical Genetics, Washington University in St. Louis, St. Louis, Missouri. 7. Department of Medicine, Boston University, Boston, Massachusetts.
Abstract
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.
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.
Authors: Jeremy Walston; Evan C Hadley; Luigi Ferrucci; Jack M Guralnik; Anne B Newman; Stephanie A Studenski; William B Ershler; Tamara Harris; Linda P Fried Journal: J Am Geriatr Soc Date: 2006-06 Impact factor: 5.562
Authors: Paola Sebastiani; Evan C Hadley; Michael Province; Kaare Christensen; Winifred Rossi; Thomas T Perls; Arlene S Ash Journal: Am J Epidemiol Date: 2009-11-12 Impact factor: 4.897
Authors: Jason L Sanders; Robert M Boudreau; Linda P Fried; Jeremy D Walston; Tamara B Harris; Anne B Newman Journal: J Am Geriatr Soc Date: 2011-08-24 Impact factor: 5.562
Authors: Amy M Matteini; M Daniele Fallin; Candace M Kammerer; Nicole Schupf; Anatoli I Yashin; Kaare Christensen; Konstantin G Arbeev; Graham Barr; Richard Mayeux; Anne B Newman; Jeremy D Walston Journal: J Gerontol A Biol Sci Med Sci Date: 2010-09-02 Impact factor: 6.053
Authors: L P Fried; C M Tangen; J Walston; A B Newman; C Hirsch; J Gottdiener; T Seeman; R Tracy; W J Kop; G Burke; M A McBurnie Journal: J Gerontol A Biol Sci Med Sci Date: 2001-03 Impact factor: 6.053
Authors: Alice M Arnold; Anne B Newman; Mary Cushman; Jingzhong Ding; Stephen Kritchevsky Journal: J Gerontol A Biol Sci Med Sci Date: 2009-04-22 Impact factor: 6.053
Authors: Anne B Newman; Nancy W Glynn; Christopher A Taylor; Paola Sebastiani; Thomas T Perls; Richard Mayeux; Kaare Christensen; Joseph M Zmuda; Sandra Barral; Joseph H Lee; Eleanor M Simonsick; Jeremy D Walston; Anatoli I Yashin; Evan Hadley Journal: Aging (Albany NY) Date: 2011-01 Impact factor: 5.682
Authors: Alexander M Kulminski; Amisha V Barochia; Yury Loika; Nalini Raghavachari; Konstantin G Arbeev; Mary K Wojczynski; Bharat Thyagarajan; Badri N Vardarajan; Kaare Christensen; Anatoliy I Yashin; Stewart J Levine Journal: PLoS One Date: 2018-11-09 Impact factor: 3.240
Authors: Chenkai Wu; Ya-Xi Li; Megan M Marron; Michelle C Odden; Anne B Newman; Jason L Sanders Journal: J Gerontol A Biol Sci Med Sci Date: 2020-09-25 Impact factor: 6.591
Authors: Megan M Marron; Tamara B Harris; Robert M Boudreau; Clary B Clish; Steven C Moore; Rachel A Murphy; Venkatesh L Murthy; Jason L Sanders; Ravi V Shah; George C Tseng; Stacy G Wendell; Joseph M Zmuda; Anne B Newman Journal: Metabolites Date: 2019-04-30