Examining the relative influence of familial, genetic, and environmental covariate information in flexible risk models
Examining the relative influence of familial, genetic, and environmental covariate information in flexible risk models
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DOI：
10.1073/pnas.0902906106
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发表时间：
2009-05-19
影响因子：
11.1
通讯作者：
Wahba, Grace
中科院分区：
文献类型：
--
作者：
Bravo, Hector Corrada;Lee, Kristine E.;Wahba, Grace
我们提出了一种研究柔性非参数风险模型中家族，遗传和环境协变量信息的相对影响的方法。我们的目标是研究这三个信息来源的相对重要性，因为它们与特定结果相关。为此，我们开发了一种将任意血统信息纳入平滑样条ANOVA（SS-ANOVA）模型中的方法。通过将谱系数据表示为正半数核矩阵，SS-Anova模型能够将logoDDS比率估算为几个变量的多组分函数：一个或多个功能组件，代表来自环境协变量的信息和/或遗传标记数据和/或遗传标记数据和/或遗传标记数据和/或遗传标记数据以及/或另一个代表谱系关系的人。我们报告了一项关于海狸大坝眼睛研究中视网膜色素异常模型的案例研究。我们的模型验证了与早期相关的黄斑变性的眼睛病变发现的流行病学的已知事实，并且在包括所有三个遗传，环境和家族数据源的模型中显示出显着提高的预测能力。案例研究还表明，仅包含两个数据源的模型，即谱系 - 环境协变量，谱系基因标记物或环境协变量基因标记物具有可比的预测能力，但比所有三个模型都少。 。该结果与遗传标记数据至少在部分数据中编码的观念一致，而家族相关性也编码共享环境数据。
We present a method for examining the relative influence of familial, genetic, and environmental covariate information in flexible nonparametric risk models. Our goal is investigating the relative importance of these three sources of information as they are associated with a particular outcome. To that end, we developed a method for incorporating arbitrary pedigree information in a smoothing spline ANOVA (SS-ANOVA) model. By expressing pedigree data as a positive semidefinite kernel matrix, the SS-ANOVA model is able to estimate a log-odds ratio as a multicomponent function of several variables: one or more functional components representing information from environmental covariates and/or genetic marker data and another representing pedigree relationships. We report a case study on models for retinal pigmentary abnormalities in the Beaver Dam Eye Study. Our model verifies known facts about the epidemiology of this eye lesion-found in eyes with early age-related macular degeneration-and shows significantly increased predictive ability in models that include all three of the genetic, environmental, and familial data sources. The case study also shows that models that contain only two of these data sources, that is, pedigree-environmental covariates, or pedigree-genetic markers, or environmental covariates-genetic markers, have comparable predictive ability, but less than the model with all three. This result is consistent with the notions that genetic marker data encode-at least in part-pedigree data, and that familial correlations encode shared environment data as well.