Table 1. Summary of top co-expression modules associated with CVD or T2D (FDR < 1% in Meta-MSEA, in column FDRmeta).
| Disease | Module ID | Tissue | Annotation | Gene No. | CAR+C4D/ DIAGRAM | JHS | FHS | WHI | WHI | WHI | Pmeta | FDRmeta |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mixed | AA | EA | EA | AA | HA | |||||||
| CVD | 4406 | O1, O2, O5 | NA | 154 | 3.32E-10 | NS | - | 2.83E-02 | 4.41E-03 | NS | 5.73E-09 | <0.01% |
| 4522 | Adp, Lv, T | Signaling by FGFR mutants | 2072 | 1.03E-04 | 1.62E-02 | - | 3.80E-02 | 5.53E-03 | 2.86E-02 | 3.39E-08 | <0.01% | |
| 4540 | O4, O5 | NA | 1233 | 9.72E-04 | NS | - | NS | 1.50E-02 | 5.52E-04 | 5.07E-07 | 0.06% | |
| 5242 | Adr | Cholesterol Biosynthesis | 306 | 4.19E-06 | 4.71E-02 | - | NS | 2.31E-02 | NS | 2.64E-06 | 0.08% | |
| 4087 | Adp, Dg | Carboxylic acid metabolic process | 158 | 2.34E-06 | NS | - | NS | 8.63E-03 | 2.17E-02 | 4.24E-06 | 0.09% | |
| 4019 | Ly | Transmembrane transport of small molecules | 2876 | 1.89E-03 | 4.46E-02 | - | NS | NS | 6.85E-04 | 7.91E-06 | 0.20% | |
| 4941 | O4, O5 | Establishment of localization | 908 | 8.97E-06 | 1.52E-02 | - | NS | NS | 3.94E-02 | 2.72E-06 | 0.21% | |
| 5023 | Ly | TCA cycle and respiratory electron transport | 2890 | NS | 6.37E-05 | - | 1.53E-03 | NS | 1.50E-02 | 1.15E-05 | 0.22% | |
| blue | O2, O4 | Cell cycle | 657 | 1.08E-02 | NS | - | NS | NS | 1.77E-04 | 3.85E-06 | 0.30% | |
| 5329 | Adr | Biological oxidations | 1028 | NS | 2.32E-02 | - | 5.01E-03 | 3.26E-02 | 2.26E-02 | 2.21E-05 | 0.35% | |
| 124 | O3, O4 | NA | 14 | NS | 1.48E-03 | - | NS | 7.05E-07 | NS | 4.86E-06 | 0.55% | |
| 4656 | O3, O4 | Cellular protein complex assembly | 371 | NS | NS | - | NS | 3.64E-03 | 2.27E-04 | 8.85E-06 | 0.67% | |
| 4147 | O5 | NA | 111 | 1.55E-02 | 2.06E-04 | - | NS | 8.85E-03 | NS | 5.72E-06 | 0.68% | |
| 4989 | Adr | Metabolism of amino acids and derivatives | 453 | 1.86E-03 | 7.41E-03 | - | NS | 3.71E-04 | NS | 7.81E-05 | 0.82% | |
| T2D | 5323 | Mn | NA | 38 | 8.68E-04 | NS | NS | 2.25E-04 | 1.05E-03 | NS | 1.58E-07 | 0.02% |
| 5250 | Adp, Dg, Mn | NA | 37 | 4.78E-05 | NS | NS | 3.01E-02 | 3.46E-07 | NS | 4.32E-07 | 0.03% | |
| 4880 | Mn | NA | 141 | 8.96E-03 | NS | 1.18E-02 | 5.06E-04 | NS | NS | 1.61E-06 | 0.06% | |
| 6872 | Mn | NA | 119 | NS | 1.26E-03 | 7.44E-03 | 7.79E-03 | NS | NS | 1.26E-06 | 0.06% | |
| 4879 | Ms | NA | 376 | 3.18E-02 | NS | 5.88E-04 | NS | 2.66E-03 | 2.20E-03 | 1.19E-06 | 0.14% | |
| 6533 | Mn | Cholesterol biosynthesis | 48 | NS | 5.02E-03 | NS | NS | NS | 1.26E-06 | 1.06E-05 | 0.25% | |
| 6977 | Bld, O3 | NA | 40 | 3.66E-02 | NS | 4.01E-05 | NS | 1.81E-02 | 4.05E-02 | 1.71E-06 | 0.39% | |
| 6675 | Mn | Cholesterol biosynthesis | 152 | 3.72E-03 | 3.35E-02 | NS | NS | NS | 2.06E-05 | 2.56E-05 | 0.52% | |
| 37 | O2 | NA | 34 | 1.94E-03 | 5.53E-03 | NS | NS | 9.38E-04 | NS | 4.95E-06 | 0.57% | |
| 4302 | Adp | NA | 40 | 2.07E-03 | NS | NS | 4.80E-03 | 4.05E-06 | NS | 9.89E-06 | 0.71% | |
| 6690 | Adr | Complement and coagulation cascades | 641 | 1.93E-02 | 1.01E-04 | NS | 2.24E-02 | NS | NS | 1.36E-05 | 0.86% | |
| 4059 | Dg | SLC mediated transmembrane transport | 51 | NS | 3.05E-02 | 5.80E-03 | NS | 1.50E-02 | NS | 1.29E-05 | 0.86% | |
| 4937 | Dg | Amino acid metabolic process | 80 | 9.21E-03 | NS | 5.88E-03 | NS | 1.37E-03 | NS | 2.11E-05 | 0.89% | |
| 5059 | Ve | TCA cycle and respiratory electron transport | 164 | 7.31E-04 | NS | 2.74E-02 | 8.66E-04 | NS | NS | 6.64E-06 | 0.95% |
Module IDs were randomly assigned IDs to co-expression modules. The annotation refers to the top functional category enriched in the co-expression modules (Bonferroni-corrected p< 0.05 based on Fisher’s exact test, number of direct overlapping genes > 5). Numbers in scientific format were p-values from MSEA or Meta-MSEA analysis, and those reaching FDR < 20% in individual cohort analysis via MSEA (not the FDRmeta in Meta-MSEA) are highlighted in bold. CAR+C4D: CARDIoGRAMplusC4D; Mixed: mixed ethnicities; JHS: Jackson Heart Study; FHS: Framingham Heart Study; WHI: Women’s Health Initiative; AA: African Americans; HA: Hispanic Americans; EA: European Americans; Pmeta and FDRmeta: p and FDR values from Meta-MSEA analysis across cohorts. Adp–adipose tissue; Adr—adrenal gland; Bld–Blood; Dg—digestive tract; Lv–liver; Ly–lymphocyte; Mn-monocyte; Ms–muscle; O1 –chromosomal distance mapping based on a 50kb window; O2 –ENCODE-based Regulome SNPs; O3 –combining all tissue-specific eQTLs into a single multi-tissue eSNP set; O4 –merging eQTL sets with Regulome data; O5 –combined mapping (distance, eQTLs, ENCODE); T–thyroid gland; Ve–vascular endothelium.