In the replication study, we recovered a robust association between OMIM genetic evidence and drug approval of a similar or greater magnitude to that originally reported [3] across several independent test sets. GWAS genetic evidence also is generally positively associated with progressing in clinical development, but the magnitude of the association is smaller and not clearly different from zero in any independent replication set. One possible reason is that recently reported GWAS variants have smaller reported effect sizes. We find evidence for this claim, but do not detect an effect of GWAS evidence effect size on approval (S13 Fig, S22 Table). There appears to be some confounding due to GWAS genes having different properties than approved drug targets. When this is controlled for using logistic regression, GWAS-supported target-indication pairs are more likely to be approved than those without a GWAS-linked gene target. This highlights the need for predictive models including target properties, work that is beginning to emerge [24].
