A link between genetic variability and clinical phenotypes is supported in human studies by several observations relating variants in regulatory gene regions to protein phenotypes or diseases [19], [20]. However, this message-passing paradigm has never been evaluated on a genome-wide basis. We therefore tested whether monocytes gene expression might mediate the effects of loci recently identified by GWAS of cardiovascular risk factors. For each locus identified in GWAS of lipid variables [21], blood pressure (BP) [22] and body mass index (BMI) [23], we selected the lead SNP or a tag SNP having an r2≥0.8 with the lead SNP in GHS data. Associations between lead/tag SNPs and corresponding risk factors were checked in all GHS subjects for whom genome-wide data was available (n = 3,175). Most previous GWAS loci for circulating lipids were replicated in our data ( Table 4 ) but only few of the findings of GWAS of BMI and BP were replicated (Table S2). This low replication is probably due to a lack of power, as the maximum R2 observed in the GWAS of BP [22] was 0.09% and the power of GHS to replicate such an association was only 38%.
