In response to the unique challenge created by high-dimensional mediators in mediation analysis, this paper presents a novel procedure for testing the nullity of the mediation effect in the presence of high-dimensional mediators. The procedure incorporates two distinct features. Firstly, the test remains valid under all cases of the composite null hypothesis, including the challenging scenario where both exposure-mediator and mediator-outcome coefficients are zero. Secondly, it does not impose structural assumptions on the exposure-mediator coefficients, thereby allowing for an arbitrarily strong exposure-mediator relationship. To the best of our knowledge, the proposed test is the first of its kind to provably possess these two features in high-dimensional mediation analysis. The validity and consistency of the proposed test are established, and its numerical performance is showcased through simulation studies. The application of the proposed test is demonstrated by examining the mediation effect of DNA methylation between smoking status and lung cancer development.

翻译：针对高维中介变量在中介分析中带来的独特挑战，本文提出了一种在存在高维中介变量时检验中介效应为零的新方法。该方法具有两个显著特征：首先，该检验在复合零假设的所有情形下均保持有效性，包括暴露-中介系数与中介-结局系数均为零的棘手场景；其次，该方法不对暴露-中介系数施加任何结构假设，从而允许暴露与中介之间存在任意强度的关联。据我们所知，所提出的检验方法是首个在高维中介分析中被证明兼具上述两个特征的方法。我们建立了该检验的有效性与一致性，并通过模拟研究展示了其数值性能。通过检验DNA甲基化在吸烟状态与肺癌发生之间的中介效应，我们进一步展示了该方法的实际应用价值。