(A) dN/dS ratio comparing large-effect family cis-eQTLs to population cis-eQTLs. We selected family eQTLs on the basis of their effect sizes relative to population eQTL effect sizes and plotted the distributions of dN/dS ratios. As a comparison, we show the distribution of dN/dS ratios for the most significant cis-eQTL genes identified only in the population (373 unrelated European individuals from the Geuvadis study) given different p value cutoffs. This is further compared to family-level genes that have rare and potentially regulatory variants (within 5 kb of the TSS, within ENCODE TF binding and DNase I hypersensitivity peaks, and with a PhyloP score > 1). We observed that for large-effect cis-eQTLs and family-level genes with a rare variant, a higher proportion were more conserved (described as the percentage of genes with a dN/dS < 0.3; lower dN/dS ratios indicate higher conservation).