Elle M Weeks, Jacob C Ulirsch, Nathan Y Cheng, Brian L Trippe, Rebecca S Fine, Jenkai Miao, Tejal A Patwardhan, Masahiro Kanai, Joseph Nasser, Charles P Fulco, Katherine C Tashman, Francois Aguet, Taibo Li, Jose Ordovas-Montanes, Christopher S Smillie, Moshe Biton, Alex K Shalek, Ashwin N Ananthakrishnan, Ramnik J Xavier, Aviv Regev, Rajat M Gupta, Kasper Lage, Kristin G Ardlie, Joel N Hirschhorn, Eric S Lander, Jesse M Engreitz, Hilary K Finucane
Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods...
July 13, 2023: Nature Genetics