Epigenetic age acceleration mediates the association between smoking and diabetes-related outcomes

Clinical Epigenetics

Table 3 Results of six DNAm markers in mediating the associations between former smoking status and four health outcomes

Outcome^a	Total effect	95% Confidence interval		p-value	Sample size
FG	0.0442	− 0.0761	0.1644	0.471	2469
HbA_1c	0.0253	− 0.0941	0.1448	0.677	2469
FEV1	− 0.0820	− 0.2155	0.0516	0.229	1576
FVC	0.0427	− 0.0667	0.1520	0.444	1576

Outcome	Mediator	Mediation effect^b	95% confidence interval		FDR^c	Proportion mediated^d (%)	Sample size
FG	HannumEAA	0.0041	− 0.0007	0.0127	0.264	9.3	2462
HbA_1c		0.0046	− 0.0005	0.0132	0.209	18.2	2462
FEV1		0.0038	− 0.0062	0.0156	0.597	− 4.6	1569
FVC		− 0.0027	− 0.0129	0.0061	0.710	− 6.3	1569
FG	PhenoEAA	0.0086	− 0.0001	0.0217	0.138	19.5	2467
HbA_1c		0.0143	0.0039	0.0286	0.021	56.5	2467
FEV1		− 0.0039	− 0.0188	0.0101	0.710	4.8	1574
FVC		− 0.0015	− 0.0146	0.0111	0.927	− 3.5	1574
FG	GrimEAA	0.0609	0.0361	0.0916	< 0.001	137.8	2464
HbA_1c		0.0710	0.0443	0.1016	< 0.001	280.6	2464
FEV1		− 0.0043	− 0.0246	0.0174	0.816	5.2	1572
FVC		− 0.0184	− 0.0372	− 0.0016	0.108	− 43.1	1572
FG	DNAm-based pack-years	0.0511	0.0133	0.0914	0.028	115.6	2415
HbA_1c		0.0667	0.0297	0.1075	< 0.001	263.6	2415
FEV1		0.0019	− 0.0370	0.0427	0.957	− 2.3	1538
FVC		0.0093	− 0.0196	0.0406	0.707	21.8	1538
FG	DNAm PAI-1	0.0268	0.0005	0.0543	0.120	60.6	2469
HbA_1c		0.0252	0.0016	0.0513	0.117	99.6	2469
FEV1		− 0.0073	− 0.0210	0.0026	0.294	8.9	1576
FVC		− 0.0132	− 0.0276	− 0.0026	0.026	− 30.9	1576
FG	DunedinPACE	0.0117	0.0021	0.0244	0.024	26.5	2468
HbA_1c		0.0199	0.0068	0.0365	0.007	78.7	2468
FEV1		0.0002	− 0.0079	0.0090	0.957	− 0.2	1575
FVC		− 0.0048	− 0.0137	0.0009	0.246	− 11.2	1575

^aBefore mediation analysis, FG and HbA_1c were natural-log transformed and then standardized as z-scores; FEV1 and FVC were standardized as z-scores
^bMediation effect is the effect of X (former smoking status) on Y (health outcome) through the mediator (DNAm marker)
^cFDR (false discovery rate) represents the FDR-adjusted p-value. Significant effects with FDR < 0.05 are marked in bold
^dProportion mediated was calculated by dividing the mediation effect by the total effect

ISSN: 1868-7083