A Module-Level Polygenic Risk Score-Based NetWAS Framework for Identifying AD Genetic Modules Mediated by Amygdala: An ADNI Study.

ABSTRACT: Network-based GWAS (NetWAS) has advanced brain imaging research by identifying genetic modules associated with brain alterations. However, how imaging risk genes exert functions in brain diseases, particularly their mediation through imaging quantitative traits (iQTs), remains underexplored. We propose a module-level polygenic risk score (MPRS)-based NetWAS framework to uncover genetic modules associated with Alzheimer's disease (AD) through the mediation of an iQT, using amygdala density as a case study. Our framework integrates genotype data, brain imaging phenotypes, clinical diagnosis of AD, and protein-protein interaction (PPI) networks to identify AD-relevant modules (ADMs) influenced by iQT-associated genetic variants. Specifically, we conducted a genome-wide association study (GWAS

SUBMITTER: Luo H 

PROVIDER: S-EPMC12249635 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature