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Bayesian shrinkage estimation of high dimensional causal mediation effects in omics studies

Author

Listed:
  • Yanyi Song
  • Xiang Zhou
  • Min Zhang
  • Wei Zhao
  • Yongmei Liu
  • Sharon L. R. Kardia
  • Ana V. Diez Roux
  • Belinda L. Needham
  • Jennifer A. Smith
  • Bhramar Mukherjee

Abstract

Causal mediation analysis aims to examine the role of a mediator or a group of mediators that lie in the pathway between an exposure and an outcome. Recent biomedical studies often involve a large number of potential mediators based on high‐throughput technologies. Most of the current analytic methods focus on settings with one or a moderate number of potential mediators. With the expanding growth of ‐omics data, joint analysis of molecular‐level genomics data with epidemiological data through mediation analysis is becoming more common. However, such joint analysis requires methods that can simultaneously accommodate high‐dimensional mediators and that are currently lacking. To address this problem, we develop a Bayesian inference method using continuous shrinkage priors to extend previous causal mediation analysis techniques to a high‐dimensional setting. Simulations demonstrate that our method improves the power of global mediation analysis compared to simpler alternatives and has decent performance to identify true nonnull contributions to the mediation effects of the pathway. The Bayesian method also helps us to understand the structure of the composite null cases for inactive mediators in the pathway. We applied our method to Multi‐Ethnic Study of Atherosclerosis and identified DNA methylation regions that may actively mediate the effect of socioeconomic status on cardiometabolic outcomes.

Suggested Citation

  • Yanyi Song & Xiang Zhou & Min Zhang & Wei Zhao & Yongmei Liu & Sharon L. R. Kardia & Ana V. Diez Roux & Belinda L. Needham & Jennifer A. Smith & Bhramar Mukherjee, 2020. "Bayesian shrinkage estimation of high dimensional causal mediation effects in omics studies," Biometrics, The International Biometric Society, vol. 76(3), pages 700-710, September.
    • Handle: RePEc:bla:biomet:v:76:y:2020:i:3:p:700-710
    DOI: 10.1111/biom.13189
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    References listed on IDEAS

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    Cited by:

    1. Yu-Bo Wang & Cuilin Zhang & Zhen Chen, 2021. "Intergenerational Associations Between Maternal Diet and Childhood Adiposity: A Bayesian Regularized Mediation Analysis," Statistics in Biosciences, Springer;International Chinese Statistical Association, vol. 13(3), pages 524-542, December.
    2. Lulu Shang & Wei Zhao & Yi Zhe Wang & Zheng Li & Jerome J. Choi & Minjung Kho & Thomas H. Mosley & Sharon L. R. Kardia & Jennifer A. Smith & Xiang Zhou, 2023. "meQTL mapping in the GENOA study reveals genetic determinants of DNA methylation in African Americans," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Jade Xiaoqing Wang & Yimei Li & Wilburn E. Reddick & Heather M. Conklin & John O. Glass & Arzu Onar‐Thomas & Amar Gajjar & Cheng Cheng & Zhao‐Hua Lu, 2023. "A high‐dimensional mediation model for a neuroimaging mediator: Integrating clinical, neuroimaging, and neurocognitive data to mitigate late effects in pediatric cancer," Biometrics, The International Biometric Society, vol. 79(3), pages 2430-2443, September.
    4. Meng An & Haixiang Zhang, 2023. "High-Dimensional Mediation Analysis for Time-to-Event Outcomes with Additive Hazards Model," Mathematics, MDPI, vol. 11(24), pages 1-11, December.
    5. Caubet, Miguel & Samoilenko, Mariia & Drouin, Simon & Sinnett, Daniel & Krajinovic, Maja & Laverdière, Caroline & Marcil, Valérie & Lefebvre, Geneviève, 2023. "Bayesian joint modeling for causal mediation analysis with a binary outcome and a binary mediator: Exploring the role of obesity in the association between cranial radiation therapy for childhood acut," Computational Statistics & Data Analysis, Elsevier, vol. 177(C).
    6. Yanyi Song & Xiang Zhou & Jian Kang & Max T. Aung & Min Zhang & Wei Zhao & Belinda L. Needham & Sharon L. R. Kardia & Yongmei Liu & John D. Meeker & Jennifer A. Smith & Bhramar Mukherjee, 2021. "Bayesian sparse mediation analysis with targeted penalization of natural indirect effects," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 70(5), pages 1391-1412, November.

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