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Post-selection inference for high-dimensional mediation analysis with survival outcomes.

作者信息

Huang Tzu-Jung, Liu Zhonghua, McKeague Ian W

机构信息

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Department of Biostatistics, Columbia University, New York, New York, USA.

出版信息

Scand Stat Theory Appl. 2025 Jun;52(2):756-776. doi: 10.1111/sjos.12770. Epub 2025 Feb 9.


DOI:10.1111/sjos.12770
PMID:40852372
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12369553/
Abstract

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.

摘要

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本文引用的文献

[1]
EFFICIENT ESTIMATION OF THE MAXIMAL ASSOCIATION BETWEEN MULTIPLE PREDICTORS AND A SURVIVAL OUTCOME.

Ann Stat. 2023-10

[2]
CoxMKF: a knockoff filter for high-dimensional mediation analysis with a survival outcome in epigenetic studies.

Bioinformatics. 2022-11-30

[3]
Large-Scale Hypothesis Testing for Causal Mediation Effects with Applications in Genome-wide Epigenetic Studies.

J Am Stat Assoc. 2022

[4]
Mediation analysis for survival data with high-dimensional mediators.

Bioinformatics. 2021-11-5

[5]
SAR1B senses leucine levels to regulate mTORC1 signalling.

Nature. 2021-8

[6]
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

CA Cancer J Clin. 2021-5

[7]
High-dimensional mediation analysis in survival models.

PLoS Comput Biol. 2020-4-17

[8]
Marginal screening for high-dimensional predictors of survival outcomes.

Stat Sin. 2019-10

[9]
Survival Rates After Lobectomy, Segmentectomy, and Wedge Resection for Non-Small Cell Lung Cancer.

Ann Thorac Surg. 2018-2-17

[10]
An adaptive resampling test for detecting the presence of significant predictors.

J Am Stat Assoc. 2015

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