01560nas a2200229   4500000000100000000000100001008004100002260001500043653002100058653003800079653003600117653002200153100002500175700002300200700002500223700002200248245006400270856005500334300000800389520091900397022001401316       2024                            d  c2024-04-1710aDrug development10aGenetic Predisposition to Disease10aGenome-wide association studies10aTarget validation1 aEric Vallabh Minikel1 aJeffery L. Painter1 aCoco Chengliang Dong1 aMatthew R. Nelson00aRefining the impact of genetic evidence on clinical success  uhttps://www.nature.com/articles/s41586-024-07316-0  a1-63 aThe cost of drug discovery and development is driven primarily by failure1, with only about 10% of clinical programmes eventually receiving approval2–4. We previously estimated that human genetic evidence doubles the success rate from clinical development to approval5. In this study we leverage the growth in genetic evidence over the past decade to better understand the characteristics that distinguish clinical success and failure. We estimate the probability of success for drug mechanisms with genetic support is 2.6 times greater than those without. This relative success varies among therapy areas and development phases, and improves with increasing confidence in the causal gene, but is largely unaffected by genetic effect size, minor allele frequency or year of discovery. These results indicate we are far from reaching peak genetic insights to aid the discovery of targets for more effective drugs.  a1476-4687