Sparse PCA corrects for cell type heterogeneity in epigenome-wide association studies

Principal component analysis on a subset of differentially methylated regions in a mixture of cell types is the basis of ReFACTor, a program to account for heterogeneity in epigenome-wide association studies (EWAS). In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) and designed for the correction of cell type heterogeneity in EWAS. ReFACTor does not require knowledge of cell counts, and it provides improved estimates of cell type composition, resulting in improved power and control for false positives in EWAS. Corresponding software is available at http://www.cs.tau.ac.il/~heran/cozygene/software/refactor.html .