RT Journal Article
SR Electronic
T1 Open Targets Genetics: An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.16.299271
DO 10.1101/2020.09.16.299271
A1 Edward Mountjoy
A1 Ellen M. Schmidt
A1 Miguel Carmona
A1 Gareth Peat
A1 Alfredo Miranda
A1 Luca Fumis
A1 James Hayhurst
A1 Annalisa Buniello
A1 Jeremy Schwartzentruber
A1 Mohd Anisul Karim
A1 Daniel Wright
A1 Andrew Hercules
A1 Eliseo Papa
A1 Eric Fauman
A1 Jeffrey C. Barrett
A1 John A. Todd
A1 David Ochoa
A1 Ian Dunham
A1 Maya Ghoussaini
YR 2020
UL http://biorxiv.org/content/early/2020/09/21/2020.09.16.299271.abstract
AB Genome-wide association studies (GWAS) have identified many variants robustly associated with complex traits but identifying the gene(s) mediating such associations is a major challenge. Here we present an open resource that provides systematic fine-mapping and protein-coding gene prioritization across 133,441 published human GWAS loci. We integrate diverse data sources, including genetics (from GWAS Catalog and UK Biobank) as well as transcriptomic, proteomic and epigenomic data across many tissues and cell types. We also provide systematic disease-disease and disease-molecular trait colocalization results across 92 cell types and tissues and identify 729 loci fine-mapped to a single coding causal variant and colocalized with a single gene. We trained a machine learning model using the fine mapped genetics and functional genomics data using 445 gold standard curated GWAS loci to distinguish causal genes from background genes at the same loci, outperforming a naive distance based model. Genes prioritized by our model are enriched for known approved drug targets (OR = 8.1, 95% CI: [5.7, 11.5]). These results will be regularly updated and are publicly available through a web portal, Open Targets Genetics (OTG, http://genetics.opentargets.org), enabling users to easily prioritize genes at disease-associated loci and assess their potential as drug targets.Competing Interest StatementThe authors have declared no competing interest.