Table 2 Summary results, highlighting top-ranked dmCpGs, GO enrichment functions and pathways per analysis
| Â | Analysis 1* 107 T1DM-ESKD (transplant and dialysis) vs 107 T1DM | Analysis 2 107 T1DM-ESKD (transplant and dialysis) vs 253 T1DM | Analysis 3* 73 T1DM-ESKD (transplant only) vs 73 T1DM | Analysis 4 73 T1DM-ESKD (transplant only) vs 253 T1DM |
|---|---|---|---|---|
Genes with dmCpGs (FDR p ≤ × 10–8) |  |  |  |  |
Number of dmCpGs | 4391 | 13,983 | 1518 | 13,739 |
Biological candidates linked to T1DM-ESKD (most significant dmCpG, p value, FC and direction in individuals with ESKD) | AFF3  cg27315109  p = 3.61 × 10–11  FC + 1.26  No additional dmCpGs ARID5B  cg22846816  p = 8.14 × 10–16  FC + 1.47  Additional dmCpGs FC↑ FKBP5b,g  cg03546163  p = 1.17 × 10–24  FC + 1.83  Additional dmCpGs FC↑ HDAC4a  cg25569341  p = 1.38 × 10–12  FC − 1.60  Additional dmCpGs FC↑ ITGALb,c  cg14889891  p = 7.06 × 10–14  FC + 2.42  Additional dmCpGs FC↑ LY9b,c  cg18920397  p = 3.57 × 10–14  FC + 2.59  Additional dmCpG FC↑ PBX1  cg20178893  p = 2.40 × 10–12  FC − 2.41  Additional dmCpG FC↓ PIM1a  cg25325512  p = 2.79 × 10–12  FC + 2.61  Additional dmCpG FC↑ RUNX3a,b,c,g  cg25616056  p = 3.69 × 10–13  FC + 2.27  Additional dmCpGs FC↑ SEPTIN9a,b,c,d,e,g  cg11328665  p = 8.07 × 10–14  FC + 1.43  Additional dmCpGs FC↑ + ↓ UPF3Ab  cg12615906  p = 8.86 × 10–16  FC + 2.32  Additional dmCpGs FC↑ | AFF3  cg16812723  p = 4.37 × 10–13  FC + 1.20  Additional dmCpGs FC↑ ARID5B  cg06456847  p = 1.54 × 10–18  FC + 1.42  Additional dmCpGs FC↑ CUX1a,f  cg25553730  p = 1.04 × 10–12  FC + 1.40  Additional dmCpGs FC↑ ELMO1a,c  cg18707120  p = 9.41 × 10–14  FC + 1.34  Additional dmCpGs FC↑ FKBP5b,g  cg03546163  p = 6.70 × 10–43  FC + 1.66  Additional dmCpGs FC↑ HDAC4a  cg25569341  p = 1.33 × 10–17  FC − 1.59  Additional dmCpGs FC↑ ITGALb,c  cg16391678  p = 3.77 × 10–14  FC + 1.27  Additional dmCpGs FC↑ LY9b,c  cg18920397  p = 3.03 × 10–13  FC + 1.99  Additional dmCpGs FC↑ PBX1  cg20178893  p = 2.56 × 10–16  FC − 2.31  Additional dmCpGs FC↑ + ↓ PIM1a  cg19799178  p = 1.62 × 10–15  FC + 3.40  Additional dmCpGs FC↑ PRKAG2a  cg07461953  p = 1.17 × 10–13  FC + 1.68  Additional dmCpGs FC↑ PTPRN2a,b,c,f  cg23361114  p = 1.66 × 10–12  FC + 1.18  Additional dmCpGs FC↑ RUNX3a,b,c,g  cg05656688  p = 1.62 × 10–14  FC + 1.36  Additional dmCpGs FC↑ SEPTIN9a,b,c,d,e,g  cg20772590  p = 2.82 × 10–15  FC + 1.50  Additional dmCpGs FC↑ UPF3Ab  cg12615906  p = 1.74 × 10–17  FC + 1.87  Additional dmCpGs FC↑ | ARID5B  cg06456847  p = 3.29 × 10–15  FC + 1.65  Additional dmCpGs FC↑ ELMO1a,c  cg00260664  p = 1.67 × 10–11  FC + 1.26  No additional dmCpGs FKBP5b,g  cg03546163  p = 1.95 × 10–15  FC + 2.20  Additional dmCpGs FC↑ RUNX3a,b,c,g  cg08544331  p = 9.98 × 10–12  FC + 1.23  No additional dmCpGs UPF3Ab  cg12615906  p = 2.29 × 10–12  FC + 2.31  Additional dmCpGs FC↑ | AFF3  cg16812723  p = 8.80 × 10–14  FC + 1.23  Additional dmCpGs FC↑ ARID5B  cg06456847  p = 3.13 × 10–20  FC + 1.50  Additional dmCpGs FC↑ CUX1a,f  cg25553730  p = 8.44 × 10–13  FC + 1.45  Additional dmCpGs FC↑ FKBP5b,g  cg03546163  p = 3.65 × 10–35  FC + 1.68  Additional dmCpGs FC↑ HDAC4a  cg07315452  p = 8.79 × 10–16  FC + 1.64  Additional dmCpGs FC↑ + ↓ ITGALb,c  cg16391678  p = 6.96 × 10–14  FC + 1.30  Additional dmCpGs FC↑  LY9b,c  cg18920397  p = 2.92 × 10–12  FC + 2.10  Additional dmCpGs FC↑ PBX1  cg21895155  p = 1.53 × 10–13  FC − 2.60  Additional dmCpG FC↓ PIM1a  cg19799178  p = 6.77 × 10–12  FC + 2.88  No additional dmCpGs RUNX3a,b,c,g  cg05656688  p = 7.38 × 10–14  FC + 1.39  Additional dmCpGs FC↑ SEPTIN9a,b,c,d,e,g  cg00871371  p = 4.73 × 10–14  FC − 3.05  Additional dmCpGs FC↑ + ↓ TAMM41  cg21194040  p = 4.75 × 10–11  FC = + 1.23  No additional dmCpGs UPF3Ab  cg12615906  p = 2.66 × 10–17  FC + 1.97  Additional dmCpGs FC↑ |
Genes with dmCpGs (FDR p ≤ × 10–8 and FC ± 2) |  |  |  |  |
Number of dmCpGs | 490 | 1112 | 132 | 1082 |
Biological candidates linked to T1DM-ESKD (most significant p value, FC and direction in individuals with ESKD) | ARID5B  cg02479789  p = 3.89 × 10–13  FC + 2.15  No additional dmCpGs HDAC4a  cg25487819  p = 1.42 × 10–11  FC + 2.54  Additional dmCpG FC↑ ITGALb,c  cg14889891  p = 7.06 × 10–14  FC + 2.42  Additional dmCpG FC↑ LY9b,c  cg18920397  p = 3.57 × 10–14  FC + 2.59  Additional dmCpG FC↑ PBX1  cg20178893  p = 2.4 × 10–12  FC − 2.41  Additional dmCpG FC↓ PIM1a  cg25325512  p = 2.79 × 10–12  FC 2.61  Additional dmCpG FC↑ RUNX3a,b,c,g  cg25616056  p = 4.7 × 10–13  FC + 2.27  Additional dmCpG FC↑ SEPTIN9a,b,c,d,e,g  cg04661929  p = 1.35 × 10–12  FC − 6.10  Additional dmCpGs FC↑ + ↓ UPF3Ab  cg12615906  p = 8.86 × 10–16  FC + 2.32  No additional dmCpGs | CUX1a,f  cg00243880  p = 9.07 × 10–12  FC + 2.10  Additional dmCpGs FC↑ FKBP5b,g  cg03591753  p = 5.72 × 10–12  FC + 14.75  No additional dmCpGs HDAC4a  cg25487819  p = 4.2 × 10–13  FC + 2.06  Additional dmCpGs FC↑ ITGALb,c  cg23954865  p = 4.39 × 10–13  FC + 8.04  No additional dmCpGs LY9b,c  cg06056332  p = 4.61 × 10–11  FC + 2.17  No additional dmCpGs PBX1  cg20178893  p = 2.56 × 10–16  FC − 2.31  Additional dmCpGs FC↓ PIM1a  cg19799178  p = 1.62 × 10–15  FC + 3.40  Additional dmCpGs FC↑ RUNX3a,b,c,g  cg03961551  p = 2.84 × 10–13  FC + 2.04  Additional dmCpGs FC↑ SEPTIN9a,b,c,d,e,g  cg04661929  p = 1.09 × 10–13  FC − 5.33  Additional dmCpGs FC↑ + ↓ | ARID5B  cg02479789  p = 1.27 × 10–12  FC + 2.28  No additional dmCpGs FKBP5b,g  cg03546163  p = 1.95 × 10–15  FC + 2.20  No additional dmCpGs UPF3Ab  cg12615906  p = 2.29 × 10–12  FC + 2.31  Additional dmCpG FC↑ | CUX1a,f  cg00243880  p = 3.18 × 10–11  FC + 2.23  Additional dmCpGs FC↑ FKBP5b,g  cg03591753  p = 1.72 × 10–11  FC + 16.14  Additional dmCpGs FC↑ HDAC4a  cg25487819  p = 6.43 × 10–13  FC + 2.21  No additional dmCpGs ITGALb,c  cg23954865  p = 9.15 × 10–13  FC + 9.03  No additional dmCpGs LY9b,c  cg18920397  p = 2.92 × 10–12  FC + 2.10  Additional dmCpG FC↑ PBX1  cg21895155  p = 1.53 × 10–13  FC − 2.59  Additional dmCpG FC↓ PIM1a  cg19799178  p = 6.77 × 10–12  FC + 2.88  No additional dmCpGs RUNX3a,b,c,g  cg03961551  p = 4.36 × 10–12  FC + 2.14  Additional dmCpG FC↑ SEPTIN9a,b,c,d,e,g  cg00871371  p = 4.73 × 10–14  FC − 3.05  Additional dmCpGs FC↑ + ↓ |
GO enrichment functions (≥ 4 and p < 0.01) |  |  |  |  |
Number of GO functions | 325 | 505 | 75 | 679 |
Top-ranked GO functions linked to T1DM-ESKD | Positive regulation of: Immune response  immune system process  leukocyte activation  lymphocyte activation  Ras protein signal transduction  T cell activation | Positive regulation of: immune response  immune system process  leukocyte activation  lymphocyte activation  Ras protein signal transduction  T cell activation | Positive regulation of: immune response  immune system process | Positive regulation of: immune response  immune system process  leukocyte activation  lymphocyte activation  melanocyte differentiation  T cell activation |
KEGG pathways (≥ 2, and p ≤ 0.01) |  |  |  |  |
Number of KEGG pathways | 11 | 16 | 1 | 14 |
Top-ranked pathways linked to T1DM-ESKD | Human T-cell leukaemia virus 1 infection Th17 cell differentiation | Human T-cell leukaemia virus 1 infection Pathways in cancer Th17 cell differentiation Transcriptional misregulation in cancer | TGF-beta signalling pathway | Human T-cell leukaemia virus 1 infection Th17 cell differentiation Transcriptional misregulation in cancer |