Title: Large-scale mediation effect signal detection in genome-wide epigenetic studies
Authors: Zhonghua Liu - The University of Hong Kong (Hong Kong) [presenting]
Abstract: In genome-wide epigenetic studies, it is often of scientific interest assessing the mediator role of DNA methylation in the causal pathway from an exposure to a clinical outcome. Mediation analysis is commonly used to answer this question. This is often done via fitting two regression models: the mediator model and the outcome model, and then the product of coefficient method to integrate information from these two models and performing hypothesis testing using Sobel's test. We propose a novel divide-aggregate test (DAT) for the composite null hypothesis for the detection of mediation effects in genome-wide epigenetic studies. We further show that the DAT can outperform the Sobel's test and the joint significance test for the detection of mediation effects in genome-wide epigenetic studies. A fast Monte Carlo correction method is also proposed for computing the p-value of the DAT method. We show via simulation studies that the DAT method controls type I error rates and outperforms the Sobel's and the joint significance test. We applied the DAT method to the Normative Aging Study to identify putative DNA methylation sites that mediate the effect of smoking on lung function.