PCSK9 is a target of several LDL-C lowering drugs currently under trial to reduce cardiovascular events34. The STARNET study35 profiled gene expression levels in cardiometabolic disease patients and showed tag SNP rs12740374 to be a strong eQTL for PCSK9 in visceral fat but not in liver. Consistent with this, our S-PrediXcan results also show a highly significant association between PCSK9 and LDL-C (p ≈ 10−13) in visceral fat and not in liver (our training algorithm did not yield a prediction model for PCSK9, i.e., there was no evidence of regulatory activity). In our results, however, the statistical evidence is much stronger in tibial nerve (p ≈ 10−27). Accordingly, in our training set (GTEx), there is much stronger evidence of regulation of this gene in tibial nerve compared to visceral fat.
