Chunk #29 — Results — Integrating Genetic and Network Data across Species to Inform GWA Discoveries — Identifying candidate susceptibility genes for coronary artery disease and LDL cholesterol levels.
Given the strong association between plasma LDL cholesterol levels and the expression of Psrc1, Sort1, and Celsr2 expression in the BXH/wt cross, we examined a recent GWAS available in the public domain in which LDL cholesterol levels were monitored [35]. A significant association was detected between rs599839 genotypes and LDL cholesterol levels in this human cohort (p = 9.0 × 10−8)[35]. Interestingly, the common allele for rs599839 was associated with higher LDL cholesterol levels [35], consistent with the association of this allele with increased CAD risk. Low SORT1, CELSR2, and PSRC1 expression levels in the HLC are also associated with the rs599839 common allele. However, given low Sort1 and Celsr2 expression levels in the BXH/wt cross are associated with increased LDL cholesterol levels (whereas low Psrc1 expression levels are associated with low LDL cholesterol levels), SORT1 and CELSR2 are the most logical candidate susceptibility gene in the 1p13.3 locus (Figure 2), although direct experimental manipulation of these two genes would be required to provide more direct functional support that these genes are involved in modulating LDL cholesterol levels. The association
