Association of whole-person polygenic component scores with Alzheimer's disease pathology

Late-Onset Alzheimer’s Disease (LOAD) is a heterogeneous disorder with complex etiology and high, largely unexplained, heritability. We used Pan-UK Biobank Consortium GWAS summary statistics to calculate polygenic scores (PRS) for 2,312 heritable traits in a sample of 2,044 elderly with clinical and post-mortem autopsy data. Weighted gene co-expression network analysis (WGCNA) was used to identify discrete correlated clusters of PRS. Eigen-PRS (ePRS) were calculated as the first principal component of PRS within each cluster. These ePRSs were then used to identify the module assocations with aging phenotypes within the ROS/MAP study cohort.