Chen Irena, Wu Zhenke, Harlow Siobán D, Karvonen-Gutierrez Carrie A, Hood Michelle M, Elliott Michael R
Department of Biostatistics, University of Michigan.
Department of Epidemiology, University of Michigan.
Ann Appl Stat. 2024 Jun;18(2):1642-1667. doi: 10.1214/23-aoas1852. Epub 2024 Apr 5.
Longitudinal biomarker data and cross-sectional outcomes are routinely collected in modern epidemiology studies, often with the goal of informing tailored early intervention decisions. For example, hormones, such as estradiol (E2) and follicle-stimulating hormone (FSH), may predict changes in womens' health during the midlife. Most existing methods focus on constructing predictors from mean marker trajectories. However, subject-level biomarker variability may also provide critical information about disease risks and health outcomes. Current literature does not provide statistical models to investigate such relationships with valid uncertainty quantification. In this paper we develop a fully Bayesian joint model that estimates subject-level means, variances, and covariances of multiple longitudinal biomarkers and uses these as predictors to evaluate their respective associations with a cross-sectional health outcome. Simulations demonstrate excellent recovery of true model parameters. The proposed method provides less biased and more efficient estimates, relative to alternative approaches that either ignore subject-level differences in variances or perform two-stage estimation where estimated marker variances are treated as observed. Empowered by the model, analyses of women's health data reveal, for the first time, that larger variability of E2 was associated with slower increases in waist circumference across the menopausal transition.
在现代流行病学研究中,纵向生物标志物数据和横断面结果通常会被收集,其目的往往是为量身定制的早期干预决策提供依据。例如,雌二醇(E2)和促卵泡激素(FSH)等激素可能预测女性中年时期的健康变化。大多数现有方法侧重于从平均标志物轨迹构建预测因子。然而,个体水平的生物标志物变异性也可能提供有关疾病风险和健康结果的关键信息。当前文献并未提供用于研究此类关系并进行有效不确定性量化的统计模型。在本文中,我们开发了一种全贝叶斯联合模型,该模型估计多个纵向生物标志物的个体水平均值、方差和协方差,并将这些作为预测因子来评估它们与横断面健康结果的各自关联。模拟结果表明该模型能出色地恢复真实模型参数。相对于那些要么忽略个体水平方差差异,要么进行两阶段估计(将估计的标志物方差视为观测值)的替代方法,所提出的方法提供的估计偏差更小且效率更高。在该模型的助力下,对女性健康数据的分析首次揭示出,E2的变异性越大,在绝经过渡期间腰围增加的速度就越慢。