Development of a human genetics-guided priority score for 19,365 genes and 399 drug indications

Áine Duffy, Ben Omega Petrazzini, David Stein, Joshua K. Park, Iain S. Forrest, Kyle Gibson, Ha My Vy, Robert Chen, Carla Márquez-Luna, Matthew Mort, Marie Verbanck, Avner Schlessinger, Yuval Itan, David N. Cooper, Ghislain Rocheleau, Daniel M. Jordan, Ron Do

Research output: Contribution to journalArticlepeer-review


Studies have shown that drug targets with human genetic support are more likely to succeed in clinical trials. Hence, a tool integrating genetic evidence to prioritize drug target genes is beneficial for drug discovery. We built a genetic priority score (GPS) by integrating eight genetic features with drug indications from the Open Targets and SIDER databases. The top 0.83%, 0.28% and 0.19% of the GPS conferred a 5.3-, 9.9- and 11.0-fold increased effect of having an indication, respectively. In addition, we observed that targets in the top 0.28% of the score were 1.7-, 3.7- and 8.8-fold more likely to advance from phase I to phases II, III and IV, respectively. Complementary to the GPS, we incorporated the direction of genetic effect and drug mechanism into a directional version of the score called the GPS with direction of effect. We applied our method to 19,365 protein-coding genes and 399 drug indications and made all results available through a web portal.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalNature Genetics
Issue number1
StatePublished - Jan 2024


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