PhenomeXcan: Mapping the genome to the phenome through the transcriptome

Milton Pividori, Padma S. Rajagopal, Alvaro Barbeira, Yanyu Liang, Owen Melia, Lisa Bastarache, YoSon Park, GTEx Consortium, Xiaoquan Wen, Hae K. Im
2020 Science Advances  
Large-scale genomic and transcriptomic initiatives offer unprecedented insight into complex traits, but clinical translation remains limited by variant-level associations without biological context and lack of analytic resources. Our resource, PhenomeXcan, synthesizes 8.87 million variants from genome-wide association study summary statistics on 4091 traits with transcriptomic data from 49 tissues in Genotype-Tissue Expression v8 into a gene-based, queryable platform including 22,515 genes. We
more » ... eveloped a novel Bayesian colocalization method, fast enrichment estimation aided colocalization analysis (fastENLOC), to prioritize likely causal gene-trait associations. We successfully replicate associations from the phenome-wide association studies (PheWAS) catalog Online Mendelian Inheritance in Man, and an evidence-based curated gene list. Using PhenomeXcan results, we provide examples of novel and underreported genome-to-phenome associations, complex gene-trait clusters, shared causal genes between common and rare diseases via further integration of PhenomeXcan with ClinVar, and potential therapeutic targets. PhenomeXcan ( provides broad, user-friendly access to complex data for translational researchers.
doi:10.1126/sciadv.aba2083 pmid:32917697 fatcat:nct4rmo7krgdjo5ln7asvcvfae