Huang Tzu-Jung, Liu Zhonghua, McKeague Ian W
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Department of Biostatistics, Columbia University, New York, New York, USA.
Scand Stat Theory Appl. 2025 Jun;52(2):756-776. doi: 10.1111/sjos.12770. Epub 2025 Feb 9.
It is of substantial scientific interest to detect mediators that lie in the causal pathway from an exposure to a survival outcome. However, with high-dimensional mediators, as often encountered in modern genomic data settings, there is a lack of powerful methods that can provide valid post-selection inference for the identified marginal mediation effect. To resolve this challenge, we develop a post-selection inference procedure for the maximally selected natural indirect effect using a semiparametric efficient influence function approach. To this end, we establish the asymptotic normality of a stabilized one-step estimator that takes the selection of the mediator into account. Simulation studies show that our proposed method has good empirical performance. We further apply our proposed approach to a lung cancer dataset and find multiple DNA methylation CpG sites that might mediate the effect of cigarette smoking on lung cancer survival.
检测处于从暴露到生存结局的因果路径中的中介因素具有重大的科学意义。然而,在现代基因组数据环境中经常遇到的高维中介因素情况下,缺乏能够为所识别的边际中介效应提供有效选择后推断的强大方法。为了解决这一挑战,我们使用半参数有效影响函数方法开发了一种用于最大选择自然间接效应的选择后推断程序。为此,我们建立了一个考虑中介因素选择的稳定一步估计量的渐近正态性。模拟研究表明,我们提出的方法具有良好的实证性能。我们进一步将我们提出的方法应用于一个肺癌数据集,发现多个DNA甲基化CpG位点可能介导吸烟对肺癌生存的影响。