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Heritability of and mortality prediction with a longevity phenotype: the healthy aging index.
Monday,2014-03-31 14:44 America/Los_Angeles — poolea2
| Title | Heritability of and mortality prediction with a longevity phenotype: the healthy aging index. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Sanders, JL, Minster, RL, M Barmada, M, Matteini, AM, Boudreau, RM, Christensen, K, Mayeux, R, Borecki, IB, Zhang, Q, Perls, T, Newman, AB |
| Journal | J Gerontol A Biol Sci Med Sci |
| Volume | 69 |
| Issue | 4 |
| Pagination | 479-85 |
| Date Published | 2014 Apr |
| ISSN | 1758-535X |
| Keywords | Aged, Aging, Cardiovascular Diseases, Female, Genetic Predisposition to Disease, Genotype, Health Behavior, Humans, Longevity, Male, Phenotype, Retrospective Studies, Risk Factors, Survival Rate, United States |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSION: </b>The HAI should be investigated further as a candidate phenotype for uncovering longevity-associated genes in humans.</p> |
| DOI | 10.1093/gerona/glt117 |
| Alternate Journal | J. Gerontol. A Biol. Sci. Med. Sci. |
| PubMed ID | 23913930 |
| PubMed Central ID | PMC3968826 |
| Grant List | U01 AG023712 / AG / NIA NIH HHS / United States P30 AG024827 / AG / NIA NIH HHS / United States U01 AG023744 / AG / NIA NIH HHS / United States P50 AG008702 / AG / NIA NIH HHS / United States AG-15928 / AG / NIA NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States P30 AG034424 / AG / NIA NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States 1F30-AG038093 / AG / NIA NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States U01AG023744 / AG / NIA NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States U01 AG023749 / AG / NIA NIH HHS / United States U01 AG023755 / AG / NIA NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States U01AG023712 / AG / NIA NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States U01AG023749 / AG / NIA NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States HHSN268201200036C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States |