It has been previously reported that cis-eQTLs based on population studies are depleted among essential genes.19 We hypothesized that if rare variation was indeed responsible for large-effect cis-eQTLs in the family, reduced impact of purifying selection on rare variants would result in family eQTLs disproportionately affecting essential genes. We tested this hypothesis in two ways: defining gene essentiality by (1) its degree of evolutionary constraint and (2) its centrality within a PPI network. To assess evolutionary constraint, we used dN/dS ratios between humans and chimps to compare large-effect cis-eQTL genes in the family to cis-eQTL genes in the population. We observed that large-effect cis-eQTL genes in the family had significantly higher conservation status than population cis-eQTL genes (Figure 3A). This was even more pronounced for genes with a rare and potentially regulatory variant within 5 kb of the TSS. By contrast, cis-eQTL genes in the population were less constrained for increasingly stringent p values.