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Table 2 Summary results, highlighting top-ranked dmCpGs, GO enrichment functions and pathways per analysis

From: Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease: an exploratory study

  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
  1. All genes included in Table 2 are reported in at least two of the categories except PRKAG2, PTPRN2 and TAMM41. Where additional dmCpGs were located within a candidate gene listed, their FCs are indicated. Approved gene symbols are included in Table 2, the gene symbols as included in the manifest file from Illumina are included in the Additional file 1
  2. CpGs cytosine-phosphate-guanine sites, dmCpGs differentially methylated CpG sites, eGFR estimated glomerular filtration rate, eQTL expression quantitative trait loci, ESKD end-stage kidney disease, FC fold change, FDR false discovery rate, GO gene ontology, KEGG Kyoto encyclopedia of genes and genomes, T1DM type 1 diabetes mellitus, T2DM type 2 diabetes mellitus
  3. aeQTL support (p < × 10–5) in American Indians (T2DM); bglomerular kidney tissue support (p < 0.05); ctubular kidney tissue support (p < 0.05); dkidney tubule support for eGFR slope (p < 0.05) using 450K data; ekidney tubule support for fibrosis (p < 0.05) using 450K data; fblood support for eGFR (p < 0.05) using 450K data; gblood support for eGFR slope (p < 0.05) using 450K data