Integrative Multiomics Insights into the Genetic and Epigenetic Architecture of Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder driven by complex genetic and molecular interactions. Despite major advances in genomics, current discoveries explain less than 40% of AD heritability, underscoring the need for integrative approaches that capture cross-omic regulation. Here, we propose a multiomics integration framework combining genomic, epigenomic, and transcriptomic data sets to identify convergent molecular signatures underlying AD pathogenesis. An integrated epigenome-wide association study-genome wide association study (EWAS-GWAS) analysis using GeneCards and VarElect identified 42 candidate genes, showing overlap between genetic susceptibility and epigenetic dysregulation. These include canonical AD loci (APOE, CLU, BIN1, PICALM, and TREM2) and novel regulatory genes such as AKT1, DOT1L, SREBF1, and PVT1. Network analysis revealed 32 nodes and 30 edges with an average node degree of 1.88 and a protein-protein interaction (PPI) enrichment p-value of 6.45 × 10