论文标题
大规模单介质假设测试的方法：可能的选择和比较
Methods for Large-scale Single Mediator Hypothesis Testing: Possible Choices and Comparisons
论文作者
论文摘要
由于零假设的复合结构H0：alpha*beta = 0（alpha：调整混杂因子后的介体对中介体的影响； beta：beta：beta：beta：beta者：调节暴露和混杂因素后的结果对介体的影响）。在本文中，我们回顾了三类用于多种中介假设检验的方法。除了这些现有方法外，我们还开发了Sobel-Comp方法，该方法使用校正后的混合参考分布来用于SOBEL的测试统计量。我们进行了广泛的仿真研究，以根据零假设和替代假设下的真实阳性速率下的假阳性率进行比较。我们发现，使用混合参考分布的方法类别可以最好地在零假设下的标称水平上保持假阳性，并且在替代假设下具有最大的真实正速率。我们使用所有方法应用了所有方法来研究从成人社会经济状况到糖化血红蛋白水平的途径中DNA甲基化位点的介导机制，该数据使用动脉粥样硬化（MESA）的多种族研究中的数据。我们还提供了在实践中选择最佳调解假设检验方法的准则。
Mediation hypothesis testing for a large number of mediators is challenging due to the composite structure of the null hypothesis, H0:alpha*beta=0 (alpha: effect of the exposure on the mediator after adjusting for confounders; beta: effect of the mediator on the outcome after adjusting for exposure and confounders). In this paper, we reviewed three classes of methods for multiple mediation hypothesis testing. In addition to these existing methods, we developed the Sobel-comp method, which uses a corrected mixture reference distribution for Sobel's test statistic. We performed extensive simulation studies to compare all six methods in terms of the false positive rates under the null hypothesis and the true positive rates under the alternative hypothesis. We found that the class of methods which uses a mixture reference distribution could best maintain the false positive rates at the nominal level under the null hypothesis and had the greatest true positive rates under the alternative hypothesis. We applied all methods to study the mediation mechanism of DNA methylation sites in the pathway from adult socioeconomic status to glycated hemoglobin level using data from the Multi-Ethnic Study of Atherosclerosis (MESA). We also provide guidelines for choosing the optimal mediation hypothesis testing method in practice.
