GWAS genetic evidence has a smaller positive effect on approval than does OMIM genetic evidence, and we only find a small beneficial effect of GWAS genetic evidence in the New Genetic validation set. One possible explanation is that most GWAS associations are to noncoding variants, and determining function from these associations will require more advanced methodology [20]. Indeed, when we only consider GWAS Catalog SNPs in high LD (R2 ≥ 0.9) to a missense variant or other variant predicted to be moderately or highly deleterious [21], the estimated effect of GWAS genetic evidence on drug target approval approaches that of OMIM. Moreover, for missense variants, we see a larger estimated effect of genetic evidence when using a more stringent LD cutoff to the lead SNP (Fig 2B).
