CIEE - Estimating and Testing Direct Effects in Directed Acyclic Graphs using Estimating Equations

In many studies across different disciplines, detailed measures of the variables of interest are available. If assumptions can be made regarding the direction of effects between the assessed variables, this has to be considered in the analysis. The functions in this package implement the novel approach CIEE (causal inference using estimating equations; Konigorski et al., 2018, <DOI:10.1002/gepi.22107>) for estimating and testing the direct effect of an exposure variable on a primary outcome, while adjusting for indirect effects of the exposure on the primary outcome through a secondary intermediate outcome and potential factors influencing the secondary outcome. The underlying directed acyclic graph (DAG) of this considered model is described in the vignette. CIEE can be applied to studies in many different fields, and it is implemented here for the analysis of a continuous primary outcome and a time-to-event primary outcome subject to censoring. CIEE uses estimating equations to obtain estimates of the direct effect and robust sandwich standard error estimates. Then, a large-sample Wald-type test statistic is computed for testing the absence of the direct effect. Additionally, standard multiple regression, regression of residuals, and the structural equation modeling approach are implemented for comparison.

Last updated

2.52 score 11 scripts 256 downloads

CJAMP - Copula-Based Joint Analysis of Multiple Phenotypes

We provide a computationally efficient and robust implementation of the recently proposed C-JAMP (Copula-based Joint Analysis of Multiple Phenotypes) method (Konigorski et al., 2019, submitted). C-JAMP allows estimating and testing the association of one or multiple predictors on multiple outcomes in a joint model, and is implemented here with a focus on large-scale genome-wide association studies with two phenotypes. The use of copula functions allows modeling a wide range of multivariate dependencies between the phenotypes, and previous results are supporting that C-JAMP can increase the power of association studies to identify associated genetic variants in comparison to existing methods (Konigorski, Yilmaz, Pischon, 2016, <DOI:10.1186/s12919-016-0045-6>; Konigorski, Yilmaz, Bull, 2014, <DOI:10.1186/1753-6561-8-S1-S72>). In addition to the C-JAMP functions, functions are available to generate genetic and phenotypic data, to compute the minor allele frequency (MAF) of genetic markers, and to estimate the phenotypic variance explained by genetic markers.

Last updated

2.04 score 11 scripts 243 downloads