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MedDiC: high dimensional mediation analysis via difference in coefficients

View ORCID ProfileQi Zhang, Zhikai Yang, Jinliang Yang
doi: https://doi.org/10.1101/2022.09.08.507169
Qi Zhang
1Department of Mathematics and Statistics, University of New Hampshire
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  • For correspondence: qi.zhang2@unh.edu
Zhikai Yang
2PhD Program in Complex Biosystems, University of Nebraska Lincoln
3Department of Agronomy and Horticulture, University of Nebraska Lincoln
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Jinliang Yang
3Department of Agronomy and Horticulture, University of Nebraska Lincoln
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Abstract

High dimensional mediation analysis has been receiving increasing popularity, largely motivated by the scientific problems in genomics and biomedical imaging. Previous literature has primarily focused on mediator selection for high dimensional mediators. In this paper, we aim at the estimation and inference of overall indirect effect for high dimensional exposures and high dimensional mediators. We propose MedDiC, a novel debiased estimator of the high dimensional overall indirect effect based on difference-in-coefficients approach. We evaluate the proposed method using intensive simulations and find that MedDiC provides valid inference and offers higher power and shorter computing time than the competitors for both low dimensional and high dimensional exposures. We also apply MedDiC to a mouse f2 dataset for diabetes study and a dataset composed of diverse maize inbred lines for flowering time, and show that MedDiC yields more biologically meaningful gene lists, and the results are reproduciable across analyses using different measures of identical biological signal or related phenotype as the outcome.

Upon the acceptance of the paper, the code will be available on GitHub (https://github.com/QiZhangStat/MedDiC).

  • Mediation Analysis
  • Debiased Estimator
  • Data Integration
  • Integrative Omics

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 12, 2022.
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MedDiC: high dimensional mediation analysis via difference in coefficients
Qi Zhang, Zhikai Yang, Jinliang Yang
bioRxiv 2022.09.08.507169; doi: https://doi.org/10.1101/2022.09.08.507169
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MedDiC: high dimensional mediation analysis via difference in coefficients
Qi Zhang, Zhikai Yang, Jinliang Yang
bioRxiv 2022.09.08.507169; doi: https://doi.org/10.1101/2022.09.08.507169

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