Regionalpcs improve discovery of DNA methylation associations with complex traits.

ABSTRACT: We have developed the regionalpcs method, an approach for summarizing gene-level methylation. regionalpcs addresses the challenge of deciphering complex epigenetic mechanisms in diseases like Alzheimer's disease. In contrast to averaging, regionalpcs uses principal components analysis to capture complex methylation patterns across gene regions. Our method demonstrates a 54% improvement in sensitivity over averaging in simulations, providing a robust framework for identifying subtle epigenetic variations. Applying regionalpcs to Alzheimer's disease brain methylation data, combined with cell type deconvolution, we uncover 838 differentially methylated genes associated with neuritic plaque burden-significantly outperforming conventional methods. Integrating methylation quantitative trait loci

SUBMITTER: Eulalio T 

PROVIDER: S-EPMC11698866 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature