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.
Funding Information
National Institutes of Health, UL1TR000430
National Institutes of Health, HHSN268201000029C
National Institutes of Health, R01DA006227-17
National Institutes of Health, DA006227
National Institutes of Health, HHSN261200800001E
National Institutes of Health, R01MH101814
National Institutes of Health, U01HG007598
National Institutes of Health, R01MH106842
National Institutes of Health, UM1HG008901
National Institutes of Health, R01GM124486
National Institutes of Health, R01HG002585
National Institutes of Health, R01HG006855
National Institutes of Health, UL1TR002550-01
National Institutes of Health, R01MH109905
National Institutes of Health, R01HG008150
National Institutes of Health, DK110919
National Institutes of Health, F32HG009987
U.S. Department of Health and Human Services, 10XS170
U.S. Department of Health and Human Services, 10XS171
U.S. Department of Health and Human Services, 10ST1035
National Institute of Mental Health, R01MH107666
National Institute of Mental Health, R01MH101822
National Institute of Mental Health, R01HL142028
National Human Genome Research Institute, 5U41HG009494
National Human Genome Research Institute, U01HG007593
National Human Genome Research Institute, R01HG010067
National Human Genome Research Institute, 1K99HG009916-01
National Human Genome Research Institute, R35HG010718
National Human Genome Research Institute, 1R01HG010480
National Human Genome Research Institute, 5T32HG000044-22
National Human Genome Research Institute, 5U41HG002371-19
National Human Genome Research Institute, R01GM122924
National Institute of Diabetes and Digestive and Kidney Diseases, P30DK020595
Gordon and Betty Moore Foundation, 4559
H2020 Marie Skaodowska-Curie Actions, 706636
Swiss National Science Foundation, 31003A_149984
Ministerio de Educacion, Cultura y Deporte, FPU15/03635
Ministerio de Economia y Competitividad, BIO2015-70777-P
Innovative Medicines Initiative, UE7-DIRECT-115317-1
Leidos Biomedical Research, BOA No. 10XS1035
