Exposure enriched outcome dependent designs for longitudinal studies of gene-environment interaction.

Exposure enriched outcome dependent designs for longitudinal studies of gene-environment interaction.
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DOI:
10.1002/sim.7332
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发表时间:
2017-08-15
影响因子:
2
通讯作者:
Park SK
Park SK
中科院分区:
医学3区
文献类型:
--
作者:
Sun Z;Mukherjee B;Estes JP;Vokonas PS;Park SK

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在许多复杂的人类疾病的发展过程中,遗传和环境因素的联合作用已越来越被认识到。尽管流行的病例对照和病例设计,纵向队列研究,可以捕捉随时间变化的结果和暴露信息,长期以来一直建议基因-环境(GXE)的相互作用。到目前为止,关于GxE相互作用纵向研究的抽样设计的文献相当有限。因此,我们考虑的设计,可以优先考虑现有队列的子样本进行回顾性基因分型的基础上,目前可用的结果,暴露和协变量数据。在这项工作中,我们提出了分层抽样的基础上总结的个人暴露和结果的轨迹,并开发了一个完整的条件似然(FCL)的估计方法,调整有偏样本。我们比较我们提出的设计和分析,通过模拟不同的采样设计和估计方法的组合的性能。我们观察到,FCL提供了改进的估计GxE相互作用和联合暴露的影响,在未校正的完整的情况下分析,和暴露富集的结果轨迹依赖的设计优于其他设计的估计效率和功率检测GxE相互作用。我们还说明了我们的设计和分析使用的数据从规范的老龄化研究,一个正在进行的纵向队列研究由退伍军人管理局于1963年发起。
Joint effects of genetic and environmental factors have been increasingly recognized in the development of many complex human diseases. Despite the popularity of case-control and case-only designs, longitudinal cohort studies that can capture time-varying outcome and exposure information have long been recommended for gene-environment (GxE) interactions. To date, literature on sampling designs for longitudinal studies of GxE interaction is quite limited. We therefore consider designs that can prioritize a subsample of the existing cohort for retrospective genotyping on the basis of currently available outcome, exposure and covariate data. In this work, we propose stratified sampling based on summaries of individual exposures and outcome trajectories, and develop a full conditional likelihood (FCL) approach for estimation that adjusts for the biased sample. We compare the performance of our proposed design and analysis to combinations of different sampling designs and estimation approaches via simulation. We observe that the FCL provides improved estimates for the GxE interaction and joint exposure effects over uncorrected complete-case analysis, and the exposure enriched outcome trajectory dependent design outperforms other designs in terms of estimation efficiency and power for detection of the GxE interaction. We also illustrate our design and analysis using data from the Normative Aging Study, an ongoing longitudinal cohort study initiated by the Veterans Administration in 1963.
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