High-Dimensional Mediation Analysis Based on Additive Hazards Model for Survival Data

Cui, Yidan and Luo, Chengwen and Luo, Linghao and Yu, Zhangsheng (2021) High-Dimensional Mediation Analysis Based on Additive Hazards Model for Survival Data. Frontiers in Genetics, 12. ISSN 1664-8021

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Abstract

Mediation analysis has been extensively used to identify potential pathways between exposure and outcome. However, the analytical methods of high-dimensional mediation analysis for survival data are still yet to be promoted, especially for non-Cox model approaches. We propose a procedure including “two-step” variable selection and indirect effect estimation for the additive hazards model with high-dimensional mediators. We first apply sure independence screening and smoothly clipped absolute deviation regularization to select mediators. Then we use the Sobel test and the BH method for indirect effect hypothesis testing. Simulation results demonstrate its good performance with a higher true-positive rate and accuracy, as well as a lower false-positive rate. We apply the proposed procedure to analyze DNA methylation markers mediating smoking and survival time of lung cancer patients in a TCGA (The Cancer Genome Atlas) cohort study. The real data application identifies four mediate CpGs, three of which are newly found.

Item Type: Article
Subjects: Science Repository > Medical Science
Depositing User: Managing Editor
Date Deposited: 20 Feb 2023 05:41
Last Modified: 04 Apr 2024 08:55
URI: http://research.manuscritpub.com/id/eprint/1586

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