Large-Scale Hypothesis Testing for Causal Mediation Effects with Applications in Genome-wide Epigenetic Studies.

ABSTRACT: In genome-wide epigenetic studies, it is of great scientific interest to assess whether the effect of an exposure on a clinical outcome is mediated through DNA methylations. However, statistical inference for causal mediation effects is challenged by the fact that one needs to test a large number of composite null hypotheses across the whole epigenome. Two popular tests, the Wald-type Sobel's test and the joint significant test using the traditional null distribution are underpowered and thus can miss important scientific discoveries. In this paper, we show that the null distribution of Sobel's test is not the standard normal distribution and the null distribution of the joint significant test is not uniform under the composite null of no mediation effect, especially in finite samples and

SUBMITTER: Liu Z 

PROVIDER: S-EPMC9385159 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature