Chunk #26 — Results — Integrating Genetic and Network Data across Species to Inform GWA Discoveries — Identifying candidate susceptibility genes for coronary artery disease and LDL cholesterol levels.
To further characterize the association of these four expression traits with CAD-associated traits, we examined the activity of these genes in the BXH/wt cross (see Methods for details), a cross designed specifically to study metabolic traits that increase risk of cardiovascular disease. The liver expression levels of Psrc1, Sort1, and Celsr2, but not Sypl2, in the BXH/wt cross were significantly associated with plasma LDL cholesterol levels (Table 4), a major CAD risk factor. However, while Psrc1 expression levels were positively correlated with plasma LDL cholesterol levels, Sort1 and Celsr2 expression levels were negatively correlated. In addition, for liver expression traits in the BXH/wt cross significantly correlated with these three genes, the Sort1 and Celsr2 correlation signatures were most significantly enriched for the GO Biological Process category “cell surface receptor linked signal transduction” (1.4-fold enrichment, p = 1.91 × 10−5, and 1.6-fold enrichment, p = 4.57 × 10−10, for Sort1 and Celsr2, respectively), while the Psrc1 correlation signature was most enriched for the “cell cycle” category (3-fold enrichment, p = 0.00044), suggesting that Sort1 and Celsr2 may be involved in similar biological processes that are distinct from processes involving Psrc1.
