Table 6.
KEGG functional enrichment analysis.
| Term | Total pathway size |
No. of genes modulated by the shared T2D/AD SNPs |
Fold enrichment |
Benjamini-corrected p-value |
Genes |
|---|---|---|---|---|---|
| hsa04540: Gap junction | 89 | 20 | 8.4 | 8.2E−11 | PRKCA, EGFR, GNAI3, GNAI2, GRB2, ADCY8, GNAI1, GNA11, ADCY5, PRKCG, SRC, PRKX, PRKCB, PRKACG, TUBB, TJP1, PRKACA, PRKACB, TUBA1A, HTR2A |
| hsa04916: Melanogenesis | 99 | 19 | 7.2 | 2.0E−09 | PRKCA, GNAI3, GNAI2, ADCY8, GNAI1, ADCY5, CREBBP, PRKCG, TCF7L2, PRKX, CTNNB1, PRKCB, PRKACG, EP300, CAMK2D, CALM3, PRKACA, PRKACB, CAMK2A, CALM2, CALM1 |
| hsa04720: Long-term potentiation | 68 | 15 | 8.2 | 4.3E−08 | PRKCA, ADCY8, CREBBP, PRKCG, PRKX, PRKCB, PRKACG, EP300, CAMK2D, CALM3, PRKACA, PRKACB, PPP3CA, CACNA1C, CAMK2A, CALM2, CALM1 |
| hsa04912: GnRH signaling pathway | 98 | 17 | 6.5 | 8.1E−08 | PRKCA, EGFR, GRB2, ADCY8, GNA11, ADCY5, SRC, PRKX, PRKCB, PRKACG, PTK2B, CAMK2D, CALM3, PRKACA, PRKACB, CACNA1C, CAMK2A, CALM2, CALM1 |
| hsa05414: Dilated cardiomyopathy | 92 | 14 | 5.7 | 9.3E−06 | ACTB, ACTC1, ADCY8, ADCY5, CACNB1, TPM2, PRKX, PRKACG, ACTG1, ITGA8, RYR2, PRKACA, PRKACB, CACNA1C |
| hsa04666: Fc gamma R-mediated phagocytosis | 95 | 14 | 5.5 | 1.2E−05 | PRKCA, DNM3, VAV3, PRKCG, ARPC5, VAV2, TTLL3, PRKCB, ARPC1A, ARPC3, ARPC2, SCIN, PLA2G4F, DNM2 |
| hsa04020: Calcium signaling pathway | 176 | 18 | 3.8 | 3.1E−05 | PRKCA, EGFR, ADCY8, GNA11, PRKCG, PRKX, PRKCB, PRKACG, PTK2B, CAMK2D, CALM3, RYR2, PRKACA, PRKACB, PPP3CA, CACNA1C, CAMK2A, CALM2, CALM1, HTR2A |
| hsa04062: Chemokine signaling pathway | 187 | 18 | 3.6 | 6.5E−05 | GNAI3, VAV3, GNAI2, GRB2, ADCY8, GNAI1, ADCY5, PF4V1, VAV2, PRKX, PRKCB, PRKACG, PTK2B, ARRB1, TIAM1, JAK2, PRKACA, PRKACB |
| hsa05110: Vibrio cholerae infection | 56 | 10 | 6.7 | 1.0E−04 | PRKCA, ACTG1, PRKACG, ACTB, TJP1, PRKCG, PRKACA, PRKACB, PRKX, PRKCB |
| hsa04310: Wnt signaling pathway | 151 | 15 | 3.7 | 2.8E−04 | PRKCA, TBL1XR1, CREBBP, PRKCG, TCF7L2, PRKX, PRKCB, CTNNB1, PRKACG, EP300, CAMK2D, PRKACA, PRKACB, PPP3CA, CAMK2A |
| hsa04010: MAPK signaling pathway | 267 | 20 | 2.8 | 4.5E−04 | PRKCA, EGFR, TAOK2, FGF14, GRB2, CACNB1, PRKCG, SRF, DAXX, FLNA, PRKX, PRKCB, PRKACG, ARRB1, PRKACA, PPP3CA, PRKACB, CACNA1C, HSPA8, PPP5C |
| hsa04914: Progesterone-mediated oocyte maturation | 86 | 11 | 4.8 | 5.1E−04 | HSP90AB1, PRKACG, GNAI3, GNAI2, GNAI1, ADCY8, ADCY5, PRKACA, PRKACB, CDK2, PRKX |
| hsa04114: Oocyte meiosis | 110 | 12 | 4.1 | 8.4E−04 | AR, ADCY8, ADCY5, PRKX, CDK2, PRKACG, CAMK2D, CALM3, PRKACA, PRKACB, PPP3CA, CAMK2A, CALM2, CALM1 |
| hsa04270: Vascular smooth muscle contraction | 112 | 12 | 4 | 8.9E−04 | PRKCA, ADCY8, ADCY5, GNA11, PRKCG, PRKX, PRKCB, PRKACG, CALM3, PRKACA, PRKACB, CACNA1C, CALM2, CALM1 |
The analysis was conducted using combined gene annotations from ANNOVAR and DAPPLE that are generated from shared T2D/AD SNPs with consistent risk alleles. The KEGG pathway analysis was performed using the DAVID tool (http://david.abcc.ncifcrf.gov/). DAVID determines the significance of a pathway by Fisher’s exact test, which directly takes into account the pathway size. Fisher’s exact test has 4 build-in parameters: total number of genes in the genome, total number of genes in the input gene set, the number of genes in the genome belonging to a specific KEGG pathway, and the number of genes in the input gene set that belong to the specific KEGG pathway. Moreover, we adopted a decoy run-based procedure to determine the truly significant pathways: 20 decoy runs were executed in addition to the “real” run. This procedure fully eliminates any remaining unwanted confounding effects, due to pathway size or other conceivable factors. Listed are 14 KEGG pathways with significant enrichments (Benjamini-corrected p-value ≤1.29E−3) of the annotated genes. Shown are the total number of genes in the pathway, the number (and the name) of annotated genes found in the pathway, fold enrichment and Benjamini-corrected p-value for enrichment.