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 developed 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 (phenomexcan.org) provides broad, user-friendly access to complex data for translational researchers.

大规模基因组和转录组学计划为复杂性状提供了前所未有的洞察力，但临床翻译仍然受到没有生物学背景和缺乏分析资源的变异水平关联的限制。我们的资源 PhenomeXcan 将来自 Genotype-Tissue Expression v8 中 49 个组织的 4091 个性状的全基因组关联研究摘要统计数据中的 887 万个变异合成到一个基于基因的可查询平台，其中包括 22,515 个基因。我们开发了一种新颖的贝叶斯共定位方法，即快速富集估计辅助共定位分析（fastENLOC），以优先考虑可能的因果基因性状关联。我们成功地复制了全表组关联研究 (PheWAS) 目录中的人类孟德尔遗传在线以及基于证据的精选基因列表中的关联。利用 PhenomeXcan 结果，我们通过 PhenomeXcan 与 ClinVar 的进一步整合，提供了新颖且未充分报告的基因组与表型关联、复杂的基因性状簇、常见疾病和罕见疾病之间共享的致病基因以及潜在的治疗靶点的示例。 PhenomeXcan (phenomexcan.org) 为转化研究人员提供了对复杂数据的广泛、用户友好的访问。