MIA: Hilary Finucane & Nathan Cheng, Polygenic priority score for GWAS gene prioritization (2021)

Models, Inference and Algorithms Broad Institute of MIT and Harvard December 1, 2021 Polygenic priority score for GWAS gene prioritization Hilary Finucane Broad Institute; Massachusetts General Hospital Nathan Cheng Finucane Lab, Broad Institute Genome-wide association studies (GWAS) are a valuable tool for understanding the biology of complex traits, but the associations found rarely point directly to causal genes. We introduce a new method to identify the causal genes by integrating GWAS summary statistics with gene expression, biological pathway, and predicted protein-protein interaction data. We further propose an approach that effectively leverages both polygenic and locus-specific genetic signals by combining results across multiple gene prioritization methods, increasing confidence in prioritized genes. Using a large set of gold standard genes to evaluate our approach, we prioritize 10,642 unique gene-trait pairs with greater than 74% estimated precision across 113 complex traits and diseases. We also present preliminary results on quantifying the confidence and uncertainty of prioritized genes, and a technique for extracting distinct disease-relevant pathways from PoPS using non-negative matrix factorization. https://www.broadinstitute.org/talks/... For more information visit: https://www.broadinstitute.org Copyright Broad Institute, 2021. All rights reserved.