Fig. 1.

Relationship between rare and common variants with respect to allele frequency and effect size. Rare variants are typically detected in specific, clinically indicated patient trio (i.e. involving testing of the affected individual and both biological parents) studies of exome sequencing, and enriched for de novo variants with individually large effects. When perturbed, the genes that carry these variants often produce phenotypes in model organisms. By contrast, common variants are usually identified in much broader genome-wide association studies (GWAS) of large unrelated cohorts. Individually, these common variants carry very small risk and are unlikely to produce a measurable phenotype when recapitulated in model organisms.