Statistical methods for mediation analysis in the era of high-throughput genomics: Current successes and future challenges

Zeng, Ping; Shao, Zhonghe; Zhou, Xiang

doi:10.1016/j.csbj.2021.05.042

Cited by 65 publications

(54 citation statements)

References 202 publications

(360 reference statements)

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“…Mediator analysis detects whether a variable plays a mediating role by statistical methods [56][57][58]. Based on former literature, mediation was tested by the causal step procedure [59][60][61], and all variables were analyzed in regression equations interpreted in Models ( 1)- (3).…”

Section: Mediator Effect Results Of Investment In Charging Stationsmentioning

confidence: 99%

An Empirical Research of the Mechanism from Electric Vehicle Production to Charging Station R&D in China

Zhang

2021

Processes

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Electric vehicles (EVs) are regarded as an effective method for dealing with serious environmental pollution. The Chinese government has implemented a series of incentives to accelerate the promotion of EV. However, the increasing production of EVs gives rise to a greater demand for better quality charging station. This study aimed to certify the impact of the production of EVs on charging station research and development (R&D) in China, with mediating effect methods and a panel fixed effect model. The conclusions derived from the study were: (1) Statistically, the production of EVs positively and significantly impacts charging station R&D; (2) the mediating role of investment in charging stations is verified in the relationship between the production of EVs and charging station R&D; (3) environmental tax can moderate the relationship between the production of EVs and charging station R&D. These results implicate, for the first time, that the production of EVs can enhance charging station R&D through the mediating role of charging station investments and the moderating role of environmental tax.

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Section: Mediator Effect Results Of Investment In Charging Stationsmentioning

confidence: 99%

An Empirical Research of the Mechanism from Electric Vehicle Production to Charging Station R&D in China

Zhang

2021

Processes

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“…However, there is no uniform dominance of one method over the others across all simulation scenarios. The performance of the methods differs according to values of π 00 , π 01 , π 10 , π 11 , the sample size and the strength of independent variables explaining the variation of the dependent variable in the two models (1) and ( 2), as captured by the variance of non-zero α, β or R 2 in models (7) and (8).…”

Section: Discussionmentioning

confidence: 99%

“…It becomes increasingly popular in recent decades in epidemiology [1,2,3,4,5]. With the advances of high-throughput technologies in genomics studies, mediation analysis often requires analyzing a large number of potential mediators [6,7]. These agnostic explorations of high-dimensional mediators allow researchers to investigate molecular traits associated with complex diseases that may be a result of socioeconomic inequalities, environmental pollution, or other exogenous factors.…”

Section: Introductionmentioning

confidence: 99%

Methods for Large-scale Single Mediator Hypothesis Testing: Possible Choices and Comparisons

Du¹,

Zhou²,

Wu³

et al. 2022

Preprint

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Mediation hypothesis testing for a large number of mediators is challenging due to the composite structure of the null hypothesis, H 0 : αβ = 0 (α: effect of the exposure on the mediator after adjusting for confounders; β: effect of the mediator on the outcome after adjusting for exposure and confounders). In this paper, we reviewed three classes of methods for multiple mediation hypothesis testing. In addition to these existing methods, we developed the Sobel-comp method, which uses a corrected mixture reference distribution for Sobel's test statistic. We performed extensive simulation studies to compare all six methods in terms of the false positive rates under the null hypothesis and the true positive rates under the alternative hypothesis. We found that the class of methods which uses a mixture reference distribution could best maintain the false positive rates at the nominal level under the null hypothesis and had the greatest true positive rates under the alternative hypothesis. We applied all methods to study the mediation mechanism of DNA methylation sites in the pathway from adult socioeconomic status to glycated hemoglobin level using data from the Multi-Ethnic Study of Atherosclerosis (MESA). We also provide guidelines for choosing the optimal mediation hypothesis testing method in practice. (word count: 196)

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“…It is increasingly used in environmental epidemiology, in particular in Developmental Origins of Health and Disease (DOHaD) research and in molecular epidemiology studies (Blum et al, 2020;Nakamura et al, 2021). With the development of high-throughput screening technologies, these methods have become key tools to investigate the pathways by which environmental exposures can affect health outcomes, and more specifically those involving epigenetic mechanisms such as DNA methylation (DNAm) variations (MacKinnon et al, 2007;VanderWeele, 2015VanderWeele, , 2016Zeng et al, 2021). High-dimensional mediation analysis is an extension of unidimensional mediation analysis including multiple mediators (Blum et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

High Dimensional Mediation Analysis: a new method applied to maternal smoking, placental DNA methylation and birth outcomes

Jumentier

Barrot

Estavoyer

et al. 2022

Preprint

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Most high dimensional mediation epigenetic studies evaluate each mediator indirect effects independently. These approaches are underpowered to detect multiple mediators and the overall indirect effect remains poorly quantified. We developed HDMAX2, an efficient algorithm for high dimensional mediation analysis using max-squared tests, considering CpGs and aggregated mediator regions. HDMAX2 outperformed existing approaches in simulated and real data, detected true mediators with increased power, and assessed the overall indirect effect of several mediators from a high dimension matrix. We showed a polygenic architecture for placenta CpGs and regions mediating the effects of maternal smoking during pregnancy on babys birth weight.

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Statistical methods for mediation analysis in the era of high-throughput genomics: Current successes and future challenges

Abstract: Graphical abstract

Cited by 65 publications

References 202 publications

An Empirical Research of the Mechanism from Electric Vehicle Production to Charging Station R&D in China

An Empirical Research of the Mechanism from Electric Vehicle Production to Charging Station R&D in China

Methods for Large-scale Single Mediator Hypothesis Testing: Possible Choices and Comparisons

High Dimensional Mediation Analysis: a new method applied to maternal smoking, placental DNA methylation and birth outcomes

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