in which are known to cause familial hypercholesterolemia44. Similarly, SREBF2, the gene encoding the TF SREBP-2, which increases the expression of LDLR, was downregulated (strongest eQTS P=3.08×10−7). The negative correlation between SREBF2 expression and measured HDL levels has been described before15, indicating that the eQTS reflects an association with an actual phenotype. Zhernakova et al.15 proposed a model where down-regulation of SREBF2 results in lower expression of its target gene, FADS2. However, we did not observe an HDL eQTS effect on FADS2 (all eQTS P>0.07), possibly because the indirect effect was too small to detect. We hypothesize that higher blood HDL levels can result in stronger reverse cholesterol transport via HDL (Figure 6d), which may result in downregulation of LDLR45.
