Garibotti Gilda, Smith Ken R, Kerber Richard A, Boucher Kenneth M
Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.
J Gerontol A Biol Sci Med Sci. 2006 Dec;61(12):1253-61. doi: 10.1093/gerona/61.12.1253.
Multigenerational pedigrees provide an opportunity for assessing the effects of unobserved environmental and genetic effects on longevity (i.e., frailty). This article applies Cox proportional hazards models to data from three-generation pedigrees in the Utah Population Database using two different frailty specification schemes that account for common environments (shared frailty) and genetic effects (correlated frailty). In a model that includes measures of familial history of longevity and both frailty effects, we find that the variance component due to genetic factors is comparable to the one attributable to shared environments: Standard deviations of the correlated and the shared frailty distributions are 0.143 and 0.186, respectively. Through simulations, we also show a greater reduction in the bias of parameter estimates for fixed covariates through the use of the correlated frailty model.
多代谱系为评估未观察到的环境和遗传效应对长寿(即衰弱)的影响提供了一个机会。本文使用两种不同的衰弱规范方案,将Cox比例风险模型应用于犹他州人口数据库中三代谱系的数据,这两种方案考虑了共同环境(共享衰弱)和遗传效应(相关衰弱)。在一个包含长寿家族史测量值和两种衰弱效应的模型中,我们发现遗传因素导致的方差分量与共享环境导致的方差分量相当:相关衰弱分布和共享衰弱分布的标准差分别为0.143和0.186。通过模拟,我们还表明,使用相关衰弱模型可以更大程度地减少固定协变量参数估计的偏差。