Heritability of and Mortality Prediction With a Longevity Phenotype: The Healthy Aging Index
Heritability of and Mortality Prediction With a Longevity Phenotype: The Healthy Aging Index
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DOI：
10.1093/gerona/glt117
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发表时间：
2014-04-01
影响因子：
5.1
通讯作者：
Newman, Anne B.
中科院分区：
文献类型：
--
作者：
Sanders, Jason L.;Minster, Ryan L.;Newman, Anne B.
背景资料。与长寿相关的基因可能会调节与年龄相关的疾病和生存的风险。健康老龄化指数(HAI)可能是长寿的一个亚型，可以在许多研究中构建用于遗传分析的HAI。我们在心血管健康研究中调查了HAI与存活率的关系，并在长寿家庭研究中调查了遗传度。HAI包括收缩压、肺肺活量、肌酐、空腹血糖和改良的Mini-Mini Status检查得分，每项得分分别为0、1或2，使用近似三分位数，从0(健康)到10(不健康)之和。在心血管健康研究中，分别用COX比例风险分析和c-统计量确定与死亡率的相关性和预测死亡的准确性。在长寿家系研究中，遗传度通过基于多基因模型的基于方差分量的家系分析来确定。心血管健康研究参与者的心血管健康指数得分(7-10)比得分较健康(0-2)的参与者高2.62倍(95%可信区间：2.22，3.10)。仅HAI对死亡的预测较好(c-统计量=0.643，95%可信区间：0.626，0.661，p<；.0001)，略逊于单独年龄(c-统计量=0.700，95%可信区间：0.684，0.717，p<；.0001；c-统计量比较，p<；.0001)。随着人口统计学、健康行为和临床合并症的调整，预测显著增加(c-统计量=0.780，95%可信区间：0.765，0.794，p<；0.0001)。在长寿家族研究中，HAI的遗传度总体为0.295(p<；.0001)，先证者为0.387(p<；.0001)，子代为0.238(p=.0004)。HAI应作为发现人类长寿相关基因的候选表型进行进一步研究。
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.