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：针对中介分析中高维中介变量带来的独特挑战，本文提出了一种检验高维中介变量中介效应为零的新方法。该方法包含两个显著特征：首先，该检验在复合零假设的所有情形下均保持有效，包括暴露-中介系数与中介-结果系数均为零的困难情形；其次，该方法不对暴露-中介系数施加结构性假设，从而允许暴露与中介之间存在任意强的关联。据我们所知，所提出的检验是首个在高维中介分析中可证明同时具备这两个特征的方法。本文建立了该检验的有效性和一致性，并通过模拟研究展示了其数值表现。通过检验DNA甲基化在吸烟状态与肺癌发展之间的中介效应，本文论证了该检验的实际应用价值。