Mapping disease loci to biological processes via joint pleiotropic and epigenomic partitioning.

ABSTRACT: Genome-wide association studies (GWAS) have identified thousands of disease-associated loci, yet their interpretation remains limited by the heterogeneity of underlying biological processes. We propose Joint Pleiotropic and Epigenomic Partitioning (J-PEP), a clustering framework that integrates pleiotropic SNP effects on auxiliary traits and tissue-specific epigenomic data to partition disease-associated loci into biologically distinct clusters. To benchmark J-PEP against existing methods, we introduce a metric-Pleiotropic and Epigenomic Prediction Accuracy (PEPA)-that evaluates how well the clusters predict SNP-to-trait and SNP-to-tissue associations using off-chromosome data, avoiding overfitting. Applying J-PEP to GWAS summary statistics for 165 diseases/traits (average N=290K),

SUBMITTER: Kerner G 

PROVIDER: S-EPMC12083580 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature