Using SAS Macros for Multiple Mediation Analysis in R.
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SUBMITTER: Fisher P
PROVIDER: S-EPMC8336624 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Mediation analysis is a useful and widely employed approach to studies in the field of psychology and in the social and biomedical sciences. The contributions of this article are several-fold. First we seek to bring the developments in mediation analysis for nonlinear models within the counterfactual framework to the psychology audience in an accessible format and compare the sorts of inferences about mediation that are possible in the presence of exposure-mediator interaction when using a counterfactual versus the standard statistical approach. Second, the work by VanderWeele and Vansteelandt (2009, 2010) is extended here to allow for dichotomous mediators and count outcomes. Third, we provide SAS and SPSS macros to implement all of these mediation analysis techniques automatically, and we compare the types of inferences about mediation that are allowed by a variety of software macros.
| S-EPMC3659198 | biostudies-literature
Project description:Mediation analysis is a statistical technique for investigating the extent to which a mediating variable transmits the relation of an independent variable to a dependent variable. Because it is useful in many fields, there have been rapid developments in statistical mediation methods. The most cutting-edge statistical mediation analysis focuses on the causal interpretation of mediated effect estimates. Cause-and-effect inferences are particularly challenging in mediation analysis because of the difficulty of randomizing subjects to levels of the mediator (MacKinnon, 2008). The focus of this paper is how incorporating longitudinal measures of the mediating and outcome variables aides in the causal interpretation of mediated effects. This paper provides useful SAS® tools for designing adequately powered studies to detect the mediated effect. Three SAS macros were developed using the powerful but easy-to-use REG, CALIS, and SURVEYSELECT procedures to do the following: (1) implement popular statistical models for estimating the mediated effect in the pretest-posttest control group design; (2) conduct a prospective power analysis for determining the required sample size for detecting the mediated effect; and (3) conduct a retrospective power analysis for studies that have already been conducted and a required sample to detect an observed effect is desired. We demonstrate the use of these three macros with an example.
| S-EPMC6133302 | biostudies-literature
Project description:SummaryTwin studies are essential for assessing disease inheritance. Data generated from twin studies are traditionally analyzed using specialized computational programs. For many researchers, especially those who are new to twin studies, understanding and using those specialized computational programs can be a daunting task. Given that SAS (Statistical Analysis Software) is the most popular software for statistical analysis, we suggest that the use of SAS procedures for twin data may be a helpful alternative and demonstrate that we can obtain similar results from SAS to those produced by specialized computational programs. This numerical validation is practically useful, because a natural concern with general statistical software is whether it can deal with data that are generated from special study designs such as twin studies and if it can test a particular hypothesis. We concluded through our extensive simulation that SAS procedures can be used easily as a very convenient alternative to specialized programs for twin data analysis.
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Project description:BackgroundMapping expression quantitative trait loci (eQTLs) has provided insight into gene regulation. Compared to cis-eQTLs, the regulatory mechanisms of trans-eQTLs are less known. Previous studies suggest that trans-eQTLs may regulate expression of remote genes by altering the expression of nearby genes. Trans-association has been studied in the mediation analysis with a single mediator. However, prior applications with one mediator are prone to model misspecification due to correlations between genes. Motivated from the observation that trans-eQTLs are more likely to associate with more than one cis-gene than randomly selected SNPs in the GTEx dataset, we developed a computational method to identify trans-eQTLs that are mediated by multiple mediators.ResultsWe proposed two hypothesis tests for testing the total mediation effect (TME) and the component-wise mediation effects (CME), respectively. We demonstrated in simulation studies that the type I error rates were controlled in both tests despite model misspecification. The TME test was more powerful than the CME test when the two mediation effects are in the same direction, while the CME test was more powerful than the TME test when the two mediation effects are in opposite direction. Multiple mediator analysis had increased power to detect mediated trans-eQTLs, especially in large samples. In the HapMap3 data, we identified 11 mediated trans-eQTLs that were not detected by the single mediator analysis in the combined samples of African populations. Moreover, the mediated trans-eQTLs in the HapMap3 samples are more likely to be trait-associated SNPs. In terms of computation, although there is no limit in the number of mediators in our model, analysis takes more time when adding additional mediators. In the analysis of the HapMap3 samples, we included at most 5 cis-gene mediators. Majority of the trios we considered have one or two mediators.ConclusionsTrans-eQTLs are more likely to associate with multiple cis-genes than randomly selected SNPs. Mediation analysis with multiple mediators improves power of identification of mediated trans-eQTLs, especially in large samples.
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Project description:For a typical medical research project based on observational data, sequential routine analyses are often essential to comprehend the data on hand and to draw valid conclusions. However, generating reports in SAS ® for routine analyses can be a time-consuming and tedious process, especially when dealing with large databases with a massive number of variables in an iterative and collaborative research environment. In this work, we present a general workflow of research based on an observational database and a series of SAS ® macros that fits this framework, which covers a streamlined data analyses and produces journal-quality summary tables. The system is generic enough to fit a variety of research projects and enables researchers to build a highly organized and concise coding for quick updates as research evolves. The result reports promote communication in collaborations and will escort the research with ease and efficiency.
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Project description:In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed.
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Project description:Mediation analysis is a methodology used to understand how and why an independent variable (X) transmits its effect to an outcome (Y) through a mediator (M). New causal mediation methods based on the potential outcomes framework and counterfactual framework are a seminal advancement for mediation analysis, because they focus on the causal basis of mediation analysis. There are several programs available to estimate causal mediation effects, but these programs differ substantially in data set up, estimation, output, and software platform. To compare these programs, an empirical example is presented, and a single mediator model with XM interaction was estimated with a continuous mediator and a continuous outcome in each program. Even though the software packages employ different estimation methods, they do provide similar causal effect estimates for mediation models with a continuous mediator and outcome. A detailed explanation of program similarities, unique features, and recommendations are discussed.
| S-EPMC7853644 | biostudies-literature
Project description:Despite the recent flourishing of mediation analysis techniques, many modern approaches are difficult to implement or applicable to only a restricted range of regression models. This report provides practical guidance for implementing a new technique utilizing inverse odds ratio weighting (IORW) to estimate natural direct and indirect effects for mediation analyses. IORW takes advantage of the odds ratio's invariance property and condenses information on the odds ratio for the relationship between the exposure (treatment) and multiple mediators, conditional on covariates, by regressing exposure on mediators and covariates. The inverse of the covariate-adjusted exposure-mediator odds ratio association is used to weight the primary analytical regression of the outcome on treatment. The treatment coefficient in such a weighted regression estimates the natural direct effect of treatment on the outcome, and indirect effects are identified by subtracting direct effects from total effects. Weighting renders treatment and mediators independent, thereby deactivating indirect pathways of the mediators. This new mediation technique accommodates multiple discrete or continuous mediators. IORW is easily implemented and is appropriate for any standard regression model, including quantile regression and survival analysis. An empirical example is given using data from the Moving to Opportunity (1994-2002) experiment, testing whether neighborhood context mediated the effects of a housing voucher program on obesity. Relevant Stata code (StataCorp LP, College Station, Texas) is provided.
| S-EPMC4339385 | biostudies-literature
Project description:Causal mediation analysis provides investigators insight into how a treatment or exposure can affect an outcome of interest through one or more mediators on causal pathway. When multiple mediators on the pathway are causally ordered, identification of mediation effects on certain causal pathways requires a sensitivity parameter to be specified. A mixed model-based approach was proposed in the Bayesian framework to connect potential outcomes at different treatment levels, and identify mediation effects independent of a sensitivity parameter, for the natural direct and indirect effects on all causal pathways. The proposed method is illustrated in a linear setting for mediators and outcome, with mediator-treatment interactions. Sensitivity analysis was performed for the prior choices in the Bayesian models. The proposed Bayesian method was applied to an adolescent dental health study, to see how social economic status can affect dental caries through a sequence of causally ordered mediators in dental visit and oral hygiene index.
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Project description:The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well-defined hypothetical interventions on the mediator. In many settings, there may be multiple ways to fix the mediator to a particular value, and these various hypothetical interventions may have very different implications for the outcome of interest. In this paper, we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator has access only to data on the particular measurement, not information on which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect, in fact, captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using 2 examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized.
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