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

Clinical Epigenetics

Table 6 Results of six DNAm markers in mediating the associations between current smokers’ pack-years and four health outcomes

Outcome ^a	Total effect	95% confidence interval		p-value	Sample size
FG	0.0114	0.0072	0.0156	1.4E-07	2452
HbA_1c	0.0063	0.0021	0.0105	0.003	2452
FEV1	− 0.0006	− 0.0052	0.0039	0.782	1563
FVC	− 0.0011	− 0.0048	0.0026	0.565	1563

Outcome	Mediator	Mediation effect^b	95% confidence interval		FDR^c	Proportion mediated^d	Sample size
FG	HannumEAA	0.0003	− 4.0E-05	0.0007	0.194	2.6	2445
HbA_1c		0.0003	− 4.0E-05	0.0007	0.178	4.8	2445
FEV1		0.0001	− 0.0002	0.0006	0.599	− 16.7	1556
FVC		− 0.0001	− 0.0004	0.0002	0.767	9.1	1556
FG	PhenoEAA	0.0003	− 2.0E-05	0.0008	0.145	2.6	2450
HbA_1c		0.0006	0.0002	0.0011	0.016	9.5	2450
FEV1		− 0.0001	− 0.0006	0.0004	0.767	16.7	1561
FVC		0.0000	− 0.0004	0.0004	0.957	0.0	1561
FG	GrimEAA	0.0064	0.0038	0.0094	< 0.001	56.1	2448
HbA_1c		0.0076	0.0049	0.0109	< 0.001	120.6	2448
FEV1		0.0001	− 0.0024	0.0025	0.957	− 16.7	1560
FVC		− 0.0008	− 0.0029	0.0013	0.622	72.7	1560
FG	DNAm-based pack-years	0.0043	− 0.0003	0.0091	0.145	37.7	2399
HbA_1c		0.0044	0.0001	0.0087	0.120	69.8	2399
FEV1		0.0013	− 0.0031	0.0062	0.744	− 216.7	1526
FVC		0.0034	0.0002	0.0072	0.108	− 309.1	1526
FG	DNAm PAI-1	0.0029	0.0017	0.0043	< 0.001	25.4	2452
HbA_1c		0.0027	0.0016	0.0041	< 0.001	42.9	2452
FEV1		− 0.0004	− 0.0012	0.0002	0.332	66.7	1563
FVC		− 0.0007	− 0.0015	− 0.0002	0.024	63.6	1563
FG	DunedinPACE	0.0014	0.0003	0.0026	0.045	12.3	2451
HbA_1c		0.0024	0.0014	0.0037	< 0.001	38.1	2451
FEV1		0.0001	− 0.0010	0.0012	0.927	− 16.7	1562
FVC		− 0.0005	− 0.0015	0.0004	0.501	45.5	1562

^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 smokers’ pack-years) 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