Table 2. Summary of the 15 key drivers and their corresponding subnetworks shared by CVD and T2D.
| Key drivers | Gene name | Sub-net size | Tissues | PCVD | FDRCVD | PT2D | FDRT2D | No. of CVD module | No. of T2D module | Suggestive genetic effect direction (CVD/T2D) | Subnetwork function |
|---|---|---|---|---|---|---|---|---|---|---|---|
| ACAT2 | Acetyl-CoA Acetyltransferase 2 | 192 | Adp, Dg, Lv, Ms, T | 1.24E-03 | 5.32% | 5.37E-03 | 4.35% | 6 | 7 | uncertain | Cell cycle; Cholesterol biosynthesis |
| ACLY | ATP Citrate Lyase | 129 | Adp, Dg, Lv, Ms | 5.96E-04 | 6.17% | 5.78E-05 | 0.47% | 5 | 6 | consistent | Cholesterol biosynthesis; Steroid biosynthesis |
| CAV1 | Caveolin 1 | 954 | Adp, Adr, Art, Dg, Ms, T, Ve | 1.24E-05 | 0.20% | 3.96E-05 | 0.32% | 7 | 4 | consistent | Immune system; Focal adhesion |
| COL6A2 | Collagen Type VI Alpha 2 Chain | 294 | Adp, Adr, Dg, Ms, T | 2.47E-03 | 4.45% | 4.97E-05 | 0.40% | 2 | 1 | consistent | Extracellular matrix |
| COX7A2 | Cytochrome C Oxidase Subunit 7A2 | 152 | Adp, Adr, Art, Bld, Dg, Lv, Ly | 2.34E-04 | 3.79% | 1.31E-04 | 1.85% | 1 | 4 | uncertain | Respiratory electron transport |
| DBI | Diazepam Binding Inhibitor | 181 | Adp, Art, Bld, Dg, Is, Lv, Ly, Ms | 1.57E-03 | 7.70% | 1.33E-02 | 6.75% | 5 | 5 | uncertain | Respiratory electron transport |
| HMGCR | 3-Hydroxy-3-Methylglutaryl-CoA Reductase | 75 | Art, Dg, Lv, Ms | 7.53E-03 | 9.09% | 7.28E-03 | 4.87% | 1 | 5 | opposite | Cholesterol biosynthesis; Steroid biosynthesis |
| IDI1 | isopentenyl-diphosphate delta isomerase 1 | 89 | Adp, Art, Dg, Is, Lv, Ms, T | 6.77E-03 | 8.95% | 2.13E-03 | 3.46% | 3 | 4 | opposite | Cholesterol biosynthesis; Steroid biosynthesis |
| IGF1 | insulin like growth factor 1 | 993 | Adr, Ms | 2.65E-03 | 5.37% | 3.71E-04 | 1.20% | 7 | 2 | consistent | Immune system; Focal adhesion |
| MCAM | melanoma cell adhesion molecule | 183 | Adp, Adr, Art, Ms, T | 2.65E-03 | 7.16% | 1.93E-03 | 5.22% | 4 | 2 | uncertain | Extracellular matrix |
| MEST | mesoderm specific transcript | 132 | Adp, Adr, Lv, Ms | 1.66E-03 | 3.36% | 6.84E-04 | 1.58% | 4 | 2 | uncertain | Fibroblast growth factor signaling |
| MSMO1 | methylsterol monooxygenase 1 | 133 | Adp, Art, Dg, Lv, Ms, T, | 2.38E-03 | 7.70% | 4.34E-05 | 0.63% | 1 | 4 | uncertain | Cholesterol biosynthesis; Steroid biosynthesis |
| PCOLCE | procollagen C-endopeptidase enhancer | 307 | Adp, Adr, Art, Hy, Lv, Ms | 1.14E-03 | 6.17% | 1.71E-06 | 0.03% | 2 | 2 | uncertain | Extracellular matrix |
| SPARC | secreted protein acidic and cysteine rich | 482 | Adp, Adr, Art, Dg, Lv, Ms, Ve | 1.81E-03 | 9.63% | 2.02E-03 | 8.18% | 5 | 3 | consistent | Extracellular matrix |
| ZFP36 | ZFP36 ring finger protein | 176 | Adp, Adr, Art, Lv, Ly, Ms | 1.42E-03 | 8.45% | 1.64E-02 | 7.69% | 3 | 3 | uncertain | Hypoxia-inducible factors; CD40 signaling |
P and FDR values were based on Meta-MSEA analysis of the KD subnetworks for enrichment of CVD or T2D GWAS signals across cohorts. The subnetwork size indicates the number of neighboring genes directly connected to a KD when all the tissue-specific networks where the KD was found are combined. No. of module columns indicate the number of CVD or T2D–associated co-expression modules from which each KD was identified. Suggestive genetic effect direction was designated “consistent” or “opposite” if the proportion of variants having consistent or opposite effect direction in CVD or T2D was statistically significant in either eQTL mapping or chromosomal distance mapping. Otherwise, “uncertain” was called. Subnetwork function was annotated based on KEGG and Reactome databases. Adp–adipose tissue; Adr—adrenal gland; Art–artery; Dg—digestive tract; Is–Islet; Hy–hypothalamus; Lv–liver; Ly–lymphocyte; Ms–muscle; T: thyroid gland; Ve: vascular endothelium.