Chunk #28 — 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 establish whether PSRC1, CELSR2, and SORT1 are closely connected in human transcriptional networks as they are in mouse, we constructed a probabilistic, causal network from the HLC and from a previously published adipose and blood tissue cohort [21], using previously described methods [25,28–30]. As depicted in Figure 3B, PSRC1, CELSR2, and SORT1 fall in the same subnetwork and are closely connected, as in the mouse network. In addition, the genes comprising this human subnetwork are enriched for genes that fall in the mouse network depicted in Figure 3A (Fisher exact test p = 1.78 × 10−8). Further, the human subnetwork is also enriched for genes falling in the MEM module (Fisher exact test p = 5.03 × 10−8), confirming the association to metabolic phenotypes detected in the mouse network. These data combined suggest that PSRC1, CELSR2, and SORT1 operate in a conserved subnetwork causally associated with cholesterol levels, obesity, diabetes and atherosclerosis.
