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

Clinical Epigenetics

Table 4 Results of six DNAm markers in mediating the associations between current smoking status and four health outcomes

Outcome ^a	Total effect	95% confidence interval		p-value	Sample size
FG	0.2533	0.1245	0.3820	1.2E-04	2469
HbA_1c	0.1293	0.0014	0.2572	0.048	2469
FEV1	0.0208	− 0.1229	0.1645	0.777	1576
FVC	0.0826	− 0.0350	0.2003	0.169	1576

Outcome	Mediator	Mediation effect^b	95% confidence interval		FDR^c	Proportion mediated^d (%)	Sample size
FG	HannumEAA	0.0116	− 0.0013	0.0267	0.183	4.6	2462
HbA_1c		0.0130	− 0.0011	0.0296	0.145	10.1	2462
FEV1		0.0053	− 0.0076	0.0210	0.590	25.5	1569
FVC		− 0.0037	− 0.0160	0.0080	0.707	− 4.5	1569
FG	PhenoEAA	0.0164	− 0.0007	0.0350	0.145	6.5	2467
HbA_1c		0.0273	0.0091	0.0483	0.013	21.1	2467
FEV1		− 0.0058	− 0.0269	0.0160	0.767	− 27.9	1574
FVC		− 0.0023	− 0.0206	0.0152	0.927	− 2.8	1574
FG	GrimEAA	0.2381	0.1457	0.3392	< 0.001	94.0	2464
HbA_1c		0.2776	0.1868	0.3744	< 0.001	214.7	2464
FEV1		− 0.0172	− 0.1029	0.0746	0.840	− 82.7	1572
FVC		− 0.0745	− 0.1468	− 0.0040	0.108	− 90.2	1572
FG	DNAm-based pack-years	0.1620	0.0448	0.2918	0.028	64.0	2415
HbA_1c		0.2115	0.0899	0.3360	0.007	163.6	2415
FEV1		0.0062	− 0.1168	0.1360	0.957	29.8	1538
FVC		0.0302	− 0.0671	0.1316	0.710	36.6	1538
FG	DNAm PAI-1	0.1018	0.0665	0.1406	< 0.001	40.2	2469
HbA_1c		0.0958	0.0634	0.1357	< 0.001	74.1	2469
FEV1		− 0.0176	− 0.0439	0.0070	0.285	− 84.6	1576
FVC		− 0.0320	− 0.0575	− 0.0103	0.016	− 38.7	1576
FG	DunedinPACE	0.0529	0.0114	0.0928	0.045	20.9	2468
HbA_1c		0.0897	0.0496	0.1347	< 0.001	69.4	2468
FEV1		0.0013	− 0.0379	0.0410	0.957	6.3	1575
FVC		− 0.0260	− 0.0600	0.0066	0.254	− 31.5	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 (current 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