Table 1.
Pathways with Significant Enrichment in the WTCCC data and Significant or Suggestive Enrichment in the DIAGRAM or non-WTCCC Replication Data
| Pathwaya | Gene Count | Genes with eSNP | FDRb |
Pathway Enrichment p Value |
Genes with p < 0.01f | eSNP |
eSNP PT2D |
||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| WTCCCc | Diagramd | Non-WTCCCe | WTCCC | Diagram | Non-WTCCCe | ||||||
| Tight junction | 186 | 39% | 0.06 | 1.20 × 10−3 | 5.40 × 10−3 | 9.61 × 10−2 | MYH1 | rs1989811 | 4.40 × 10−5 | 1.60 × 10−4 | 5.23 × 10−2 |
| MYH2 | rs2097657 | 4.40 × 10−5 | 4.30 × 10−4 | 1.12 × 10−1 | |||||||
| EXOC4 | rs6976491 | 2.10 × 10−4 | 6.70 × 10−4 | 8.39 × 10−2 | |||||||
| CLDN23 | rs2976929 | 4.30 × 10−4 | 6.90 × 10−3 | 3.64 × 10−1 | |||||||
| CSNK2B | rs1077394 | 5.50 × 10−4 | 2.10 × 10−5 | 1.85 × 10−3 | |||||||
| Adherens junction | 110 | 45% | 0.18 | 7.40 × 10−3 | 2.40 × 10−2 | 8.08 × 10−2 | CSNK2B | rs1077394 | 5.50 × 10−4 | 2.10 × 10−5 | 1.85 × 10−3 |
| Calcium signaling pathway | 239 | 39% | 0.19 | 9.60 × 10−3 | 1.60 × 10−2 | 3.20 × 10−1 | PDE1A | rs6711862 | 2.30 × 10−2 | 1.70 × 10−3 | 1.18 × 10−2 |
| GRIN2C | rs6501741 | 3.00 × 10−2 | 7.10 × 10−3 | 4.73 × 10−2 | |||||||
| ITPR1 | rs4684443 | 1.70 × 10−2 | 8.00 × 10−3 | 7.95 × 10−2 | |||||||
| AGTR1 | rs16861027 | 3.30 × 10−2 | 8.30 × 10−3 | 5.22 × 10−2 | |||||||
| Hematopoietic cell lineage | 120 | 33% | 0.19 | 1.70 × 10−2 | 3.60 × 10−2 | 3.66 × 10−1 | CR1 | rs1323720 | 6.30 × 10−3 | 6.30 × 10−3 | 1.13 × 10−1 |
| HLA-DQA1/ HLA-DRB1/ HSPA1B | rs1077394 | 5.50 × 10−4 | 2.10 × 10−5 | 1.85 × 10−3 | |||||||
| HLA-G | rs2256902 | 8.10 × 10−4 | 1.10 × 10−3 | 6.80 × 10−2 | |||||||
| Complement and coagulation cascades | 108 | 46% | 0.19 | 1.80 × 10−2 | 5.30 × 10−2 | 1.65 × 10−2 | CR1 | rs1323720 | 6.30 × 10−3 | 6.30 × 10−3 | 1.13 × 10−1 |
| C4A/B | rs1077394 | 5.50 × 10−4 | 2.10 × 10−5 | 1.85 × 10−3 | |||||||
| C5 | rs10818503 | 4.50 × 10−3 | 8.80 × 10−3 | 1.79 × 10−1 | |||||||
| PPAR signaling pathway | 92 | 43% | 0.2 | 2.90 × 10−2 | 2.70 × 10−2 | 6.46 × 10−1 | PPARD | rs9368849 | 7.60 × 10−4 | 1.70 × 10−3 | 1.02 × 10−1 |
| SCD | rs11190462 | 9.20 × 10−2 | 6.10 × 10−3 | 1.45 × 10−2 | |||||||
| Ether lipid metabolism | 45 | 51% | 0.2 | 3.10 × 10−2 | 2.40 × 10−1 | 8.03 × 10−2 | AGPAT6 | rs919035 | 1.40 × 10−1 | 3.20 × 10−3 | 3.75 × 10−3 |
| TGF-β signaling pathway | 134 | 45% | 0.2 | 3.50 × 10−2 | 2.10 × 10−2 | 5.44 × 10−2 | RBL2 | rs4784312 | 2.30 × 10−4 | 8.80 × 10−4 | 1.00 × 10−1 |
| INHBB | rs11677557 | 5.60 × 10−1 | 3.50 × 10−3 | 3.44 × 10−4 | |||||||
| SMURF2 | rs17401012 | 1.50 × 10−1 | 9.20 × 10−3 | 1.42 × 10−2 | |||||||
| Antigen processing and presentation | 119 | 41% | 0.46 | 3.90 × 10−2 | 3.34 × 10−4 | 2.12 × 10−3 | HLA-DQA1/ HLA-DRB1/ HSPA1B | rs1077394 | 5.50 × 10−4 | 2.10 × 10−5 | 1.85 × 10−3 |
| HLA-B/ HSPA1L | rs2260000 | 1.80 × 10−3 | 7.20 × 10−4 | 2.98 × 10−2 | |||||||
| HLA-C | rs2596503 | 3.20 × 10−3 | 2.40 × 10−3 | 6.68 × 10−2 | |||||||
| HLA-E | rs2523589 | 1.90 × 10−3 | 1.40 × 10−4 | 5.48 × 10−3 | |||||||
| HLA-G | rs2256902 | 8.10 × 10−4 | 1.10 × 10−3 | 6.80 × 10−2 | |||||||
| HLA-DMB | rs3134954 | 3.20 × 10−1 | 5.70 × 10−3 | 2.43 × 10−3 | |||||||
Pathway gene sizes, p values, FDRs, validation p values, and genes with eSNPs having PT2D ≤ 0.01 in DIAGRAM are presented for the nine pathways with significant (p ≤ 0.05) enrichment in the WTCCC data and significant or suggestive (p ≤ 0.10) enrichment in the DIAGRAM or non-WTCCC data.
Pathways are from the Kyoto Encyclopedia of Genes and Genomes (KEGG).
FDR is based on 10,000 permutations and 110 pathways tested in total, using the WTCCC T2D GWAS samples.
p values are based on 10,000 permutations, using the WTCCC T2D GWAS samples.
DIAGRAM Validation p values are based on Komogorov one sided statistic test compared to a uniform distribution, using DIAGRAM T2D GWAS results.
Non-WTCCC Validation p values are based on Komogorov one sided statistic test compared to a uniform distribution, using meta-analysis p values derived based DIAGRAM samples excluding WTCCC detection samples.
Only pathway genes whose representative eSNPs reached DIAGRAM PT2D ≤ 0.01 are listed here, although there are many more eSNPs associated with each pathway. All representative eSNPs of each pathway are listed in Table S2.