Fig. 2

Relationship between effect size and allele frequency (adopted from [25, 26]). Extremely rare genetic variants with large effect sizes (upper left, strong red color) are often identified in family-based genome-wide linkage analyses. Common genetic variants with small effect sizes (lower right, strong green color) have been identified in traditional GWAS (including only common variants). Rare variants with small effects (lower left) are difficult to identify. Whereas common genetic variants with large effects (upper right) have been identified using both linkage analysis and GWAS, however these are highly unusual for common diseases