The identification of genetic variants that contribute to human disease has facilitated the development of highly efficacious and safe therapeutic agents3–5. Drug candidates targeting genes with evidence of human disease causality are in fact substantially more likely to be approved6,7. Exome sequencing has revolutionized our understanding of rare diseases, uncovering causal rare variants for hundreds of these disorders. However, most efforts for complex human diseases and traits have relied on genome-wide association studies (GWAS), which focus on common variants. Compared with rare variants, common variants tend to confer smaller effect sizes and can be difficult to map to causal genes8.
