Heritability of and mortality prediction with a longevity phenotype: The healthy aging index

Jason L. Sanders, Ryan L. Minster, M. Michael Barmada, Amy M. Matteini, Robert M. Boudreau, Kaare Christensen, Richard Mayeux, Ingrid B. Borecki, Qunyuan Zhang, Thomas Perls, Anne B. Newman

Research output: Contribution to journalArticle

Abstract

Background.Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI's association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study.Methods.The HAI includes systolic blood pressure, pulmonary vital capacity, creatinine, fasting glucose, and Modified Mini-Mental Status Examination score, each scored 0, 1, or 2 using approximate tertiles and summed from 0 (healthy) to 10 (unhealthy). In Cardiovascular Health Study, the association with mortality and accuracy predicting death were determined with Cox proportional hazards analysis and c-statistics, respectively. In Long Life Family Study, heritability was determined with a variance component-based family analysis using a polygenic model.Results.Cardiovascular Health Study participants with unhealthier index scores (7-10) had 2.62-fold (95% confidence interval: 2.22, 3.10) greater mortality than participants with healthier scores (0-2). The HAI alone predicted death moderately well (c-statistic = 0.643, 95% confidence interval: 0.626, 0.661, p <. 0001) and slightly worse than age alone (c-statistic = 0.700, 95% confidence interval: 0.684, 0.717, p <. 0001; p <. 0001 for comparison of c-statistics). Prediction increased significantly with adjustment for demographics, health behaviors, and clinical comorbidities (c-statistic = 0.780, 95% confidence interval: 0.765, 0.794, p <. 0001). In Long Life Family Study, the heritability of the HAI was 0.295 (p <. 0001) overall, 0.387 (p <. 0001) in probands, and 0.238 (p =. 0004) in offspring.Conclusion.The HAI should be investigated further as a candidate phenotype for uncovering longevity-associated genes in humans.

Original languageEnglish (US)
Pages (from-to)479-485
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume69
Issue number4
DOIs
StatePublished - Jan 1 2014

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Keywords

  • Epidemiology
  • Genetics
  • Longevity
  • Successful aging.

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Sanders, J. L., Minster, R. L., Barmada, M. M., Matteini, A. M., Boudreau, R. M., Christensen, K., Mayeux, R., Borecki, I. B., Zhang, Q., Perls, T., & Newman, A. B. (2014). Heritability of and mortality prediction with a longevity phenotype: The healthy aging index. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 69(4), 479-485. https://doi.org/10.1093/gerona/glt117