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.
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