(B) Enrichment of potentially regulatory variants depends on allele frequency and relative effect sizes. We ranked genes (x axis) on the basis of how often their effect sizes in the family were greater than their effect sizes in the population subsamples, which is also 1 − their empirical p values (see Material and Methods). Variants are restricted to those within <100 kb of the TSS, within ENCODE TF binding and DNase I hypersensitivity peaks, and with a PhyloP score > 1. We observed that variant enrichment was dependent on whether the variant was rare (blue) or not (gray). We calculated enrichment by dividing the proportion of genes with such an annotated rare variant in each effect-size bin by the proportion of genes with an annotated rare variant across all effect-size bins.