ArticleNature communications2025
regionalpcs improve discovery of DNA methylation associations with complex traits.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Pathway-level epigenetic modeling illuminates the methylation architecture to asthma risk across tissues.Epigenetics & chromatin · 2026Article
- Focus on single-gene effects limits discovery and interpretation of complex-trait-associated variants.American journal of human genetics · 2026Article
- fSuSiE enables fine-mapping of QTLs from genome-scale molecular profiles.bioRxiv : the preprint server for biology · 2025Article
- Integrative multi-omics QTL colocalization maps regulatory architecture in aging human brain.medRxiv : the preprint server for health sciences · 2025Article
- regionalpcs improve discovery of DNA methylation associations with complex traits.Nature communications · 2025Article
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7 authors.
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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 with genome-wide association studies identified 17 genes with potential causal roles in Alzheimer's disease risk, including MS4A4A and PICALM. Available in the Bioconductor package regionalpcs, our approach facilitates a deeper understanding of the epigenetic landscape in Alzheimer's disease and opens avenues for research into complex diseases.
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