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The goodness–of–fit test can be used to decide whether a population fits a given distribution, but it will not suffice to decide whether two populations follow the same unknown distribution. A different test, called the test for homogeneity, can be used to conclude whether two populations have the same distribution. To calculate the test statistic for a test for homogeneity, follow the same procedure as with the test of independence. The hypotheses for the test for homogeneity can...
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The test of independence is a chi-square-based test used to determine whether two variables or factors are independent or dependent. This hypothesis test is used to examine the independence of the variables. One can construct two qualitative survey questions or experiments based on the variables in a contingency table. The goal is to see if the two variables are unrelated (independent) or related (dependent). The null and alternative hypotheses for this test are:
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Testing for the indirect effect under the null for genome-wide mediation analyses.

Richard Barfield1, Jincheng Shen1, Allan C Just2

  • 1Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.

Genetic Epidemiology
|October 31, 2017
PubMed
Summary

Common mediation tests are overly conservative in genome-wide studies when exposure and mediator, or mediator and outcome, lack association. Caution is advised when using these methods for indirect effect testing in genetic epidemiology.

Keywords:
DNA methylation, epigenetics, hypothesis testing, type I errorcomposite null

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Area of Science:

  • Epidemiology
  • Genetics
  • Biostatistics

Background:

  • Mediation analysis assesses indirect effects of exposures on outcomes via intermediate variables.
  • Genome-wide studies increasingly use mediation analysis with genomic measures like DNA methylation (DNAm).
  • Testing indirect effects is complex due to a composite null hypothesis.

Purpose of the Study:

  • Evaluate commonly used mediation testing methods for indirect effects in genome-wide studies.
  • Assess method performance when exposure-mediator or mediator-outcome associations are absent.
  • Provide guidance on applying mediation tests in genetic epidemiology.

Main Methods:

  • Simulation studies to evaluate mediation testing methods.
  • Epigenome-wide mediation association study in the Normative Aging Study.
  • Analysis of DNA methylation as a mediator of pack-years' effect on FEV1.

Main Results:

  • Common mediation tests are overly conservative when exposure-mediator or mediator-outcome associations are null.
  • This null scenario is frequent in genome-wide mediation studies.
  • Demonstrated conservative performance of standard tests in simulations.

Conclusions:

  • Standard mediation tests require caution in genome-wide settings due to potential conservativeness.
  • Findings highlight the need for method refinement for indirect effect testing in genetic studies.
  • Results inform best practices for mediation analysis in large-scale genomic research.