DNA Methylation Near DLGAP2 May Mediate the Relationship between Family History of Type 1 Diabetes and Type 1 Diabetes Risk
Table 3
Decomposed direct and indirect causal mediation effects for the effect of family history of T1D (exposure) on T1D risk (outcome) mediated through DNA methylation (mediator).
CpG
DMR/DMP
Near gene
Affected mother
Affected father or sibling
PNIE
TNDE
PNIE
TNDE
OR
Lower 95% CI
Upper 95% CI
OR
Lower 95% CI
Upper 95% CI
OR
Lower 95% CI
Upper 95% CI
OR
Lower 95% CI
Upper 95% CI
Imprinted region (DLGAP2)
cg02946697
DMR13
CTD-2281E23.1
1.50
0.89
2.56
5.18
0.12
223.14
0.97
0.79
1.19
3.76
1.59
8.89
cg08285446
DMR13
CTD-2281E23.1
1.35
0.86
2.10
1.30
0.35
4.91
0.98
0.80
1.20
3.52
1.55
8.01
cg24513387
DMR13
CTD-2281E23.1
1.25
0.85
1.85
1.72
0.35
8.60
1.05
0.88
1.25
3.21
1.44
7.17
cg25674613
DMR13
CTD-2281E23.1
1.65
0.94
2.88
1.07
0.27
4.19
1.05
0.78
1.40
3.08
1.31
7.21
cg00565786
DMR10
CTD-2281E23.2
1.98
1.06
3.71
1.65
0.16
16.62
1.22
0.84
1.78
2.84
1.16
6.99
cg27509052
DMR10
CTD-2281E23.2
1.92
0.99
3.73
0.90
0.20
4.08
1.12
0.74
1.70
2.77
1.12
6.83
cg19309499
DMP
CTD-2281E23.3
1.59
0.95
2.67
1.12
0.34
3.70
0.98
0.73
1.31
3.87
1.59
9.39
cg11192059
DMR9
DLGAP2
1.63
0.95
2.79
2.49
0.16
39.10
1.02
0.74
1.42
2.97
1.30
6.78
cg22763586
DMR9
DLGAP2
1.76
0.93
3.32
0.99
0.24
4.19
1.04
0.72
1.51
3.13
1.33
7.37
cg27351978
DMR9
DLGAP2
2.37
1.08
5.17
0.69
0.13
3.59
1.10
0.70
1.72
2.67
1.06
6.73
cg16922753
DMR5
ERICH1-AS1
1.39
0.79
2.42
1.25
0.38
4.19
1.07
0.88
1.30
3.34
1.37
8.17
cg19530281
DMR5
ERICH1-AS1
1.78
0.89
3.56
0.92
0.24
3.58
1.13
0.81
1.59
3.01
1.17
7.76
Nonimprinted region (HOPX)
cg00493422
DMR2
HOPX
1.05
0.70
1.58
1.89
0.61
5.85
1.31
0.91
1.89
2.77
1.18
6.48
cg04085076
DMR2
HOPX
1.04
0.72
1.51
2.12
0.57
7.87
1.11
0.82
1.49
3.29
1.41
7.65
cg06771126
DMR2
HOPX
1.02
0.74
1.41
2.19
0.58
8.26
1.08
0.83
1.43
3.33
1.46
7.61
cg16975863
DMR2
HOPX
1.29
0.73
2.28
1.36
0.41
4.57
1.40
0.91
2.17
2.45
0.96
6.24
cg25456368
DMR2
HOPX
1.13
0.82
1.54
2.02
0.54
7.60
1.22
0.90
1.66
2.90
1.27
6.64
PNIE (pure natural indirect effect) = the effect of T1D family history on T1D risk that acts through DNA methylation. TNDE (total natural direct effect) = the effect of T1D family history on T1D risk that is unexplained by DNA methylation. DMR, differentially methylated region, DMR identifier Johnson et al. [13], Sci Rep. DMP, differentially methylated position. Bold = probes displaying evidence of significant mediation through methylation for children of affected mothers (significant PNIE, nonsignificant TNDE) but not for children of affected fathers or siblings (nonsignificant PNIE, significant TNDE).
