A0382
Title: Testing cell-type-specific mediation effects in genome-wide epigenetic studies
Authors: Zhonghua Liu - The University of Hong Kong (Hong Kong) [presenting]
Abstract: In current epigenome-wide mediation analysis, DNA methylation CpGsites that mediate a causal effect can only be identified. Because the methylation values are mixed from a heterogeneous population of cells, it is crucial to get fine-grained results by detecting mediation CpG sites in a cell-type-specific way. However, there is a lack of methods and software for testing cell-type-specific mediation effects. We propose a novel method, MICS (Methylation In a Cell-type-Specific fashion), to identify cell-type-specific mediation effects in genome-wide epigenetic studies. MICS first estimates the cellular compositions via a reference methylation matrix, then uses the estimated cell proportions to obtain the cell-type-specific p-values with respect to the exposure effects on the CpG sites as well as the methylation effects on the outcome, and finally combines the two p-value matrices using a joint-significance-followed by-squaring procedure. We conduct simulation studies to demonstrate that our method has correct type I error control and is powerful and robust under practical settings. We also apply our method to the Normative Aging Study and identify three CpG sites in the monocytes that might mediate the effects of smoking on lung function.
