Confounder detection in linear mediation models: Performance of kernel-based tests of independence
Related Experiment Video
Updated: Jan 27, 2026

Selection-dependent and Independent Generation of CRISPR/Cas9-mediated Gene Knockouts in Mammalian Cells
Published on: June 16, 2017
Wolfgang Wiedermann1, Xintong Li2
1Department of Educational, School, and Counseling Psychology, University of Missouri, Columbia, MO, USA. wiedermannw@missouri.edu.
Abstract:
It is well-known that the identification of direct and indirect effects in mediation analysis requires strong unconfoundedness assumptions. Even when the predictor is under experimental control, unconfoundedness assumptions must be imposed on the mediator-outcome relation in order to guarantee valid indirect-effect identification. Researchers are therefore advised to test for unconfoundedness when estimating mediation effects. Significance tests to evaluate unconfoundedness usually rely on an instrumental variable (IV)-that is, a variable that is nonindependent of the explanatory variable and, at the same time, independent of all exogenous factors that affect the outcome when the explanatory variable is held constant. Because IVs may be hard to come by, the present study shows that confounders of the mediator-outcome relation can be detected without making use of IVs when variables are nonnormal. We show that kernel-based tests of independence are able to detect confounding under nonnormality. Results from a simulation study are presented that suggest that these tests perform well in terms of Type I error protection and statistical power, independent of the distribution or measurement level of the confounder. A real-world data example from the Job Search Intervention Study (JOBS II) illustrates how the presented approach can be used to minimize the risk of obtaining biased indirect-effect estimates. The data requirements and role of unconfoundedness tests as diagnostic tools are discussed. A Monte Carlo-based power analysis tool for sample size planning is also provided.
Related Concept Videos
Confounding in Epidemiological Studies
Introduction to Test of Independence
The test statistic for a test of independence is similar to that of a goodness-of-fit test:
Hypothesis Test for Test of Independence
H0: The two variables (factors)...
Strategies for Assessing and Addressing Confounding
Confounding can be addressed at both the design phase of a study and through analytical methods after data...
Analysis Methods of Pharmacokinetic Data: Model and Model-Independent Approaches
The model approach uses mathematical models to describe changes in drug concentration over time. Pharmacokinetic models help characterize drug behavior in patients, predict drug concentration in the body fluids, calculate optimum dosage regimens, and evaluate the risk of toxicity. However, ensuring that the model fits the experimental data accurately...
Law of Independent Assortment

