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

Clinical Epigenetics

Table 7 Results of six DNAm markers in mediating the associations between years since smoking cessation and four health outcomes

Outcome ^a	Total effect	95% confidence interval		p-value	Sample size
FG	0.0012	− 0.0123	0.0147	0.859	300
HbA_1c	− 0.0018	− 0.0150	0.0115	0.795	300
FEV1	0.0005	− 0.0143	0.0154	0.947	193
FVC	− 0.0036	− 0.0147	0.0074	0.516	193

Outcome	Mediator	Mediation effect^b	95% confidence interval		FDR^c	Proportion mediated^d (%)	Sample size
FG	HannumEAA	− 0.0008	− 0.0032	0.0007	0.566	− 66.7	299
HbA_1c		− 0.0011	− 0.0037	0.0008	0.447	61.1	299
FEV1		0.0002	− 0.0028	0.0035	0.957	40.0	192
FVC		0.0014	− 0.0001	0.0041	0.191	− 38.9	192
FG	PhenoEAA	− 0.0017	− 0.0049	0.0006	0.273	− 141.7	300
HbA_1c		− 0.0020	− 0.0055	0.0003	0.194	111.1	300
FEV1		0.0056	0.0013	0.0113	0.026	1120.0	193
FVC		0.0033	0.0006	0.0068	0.055	− 91.7	193
FG	GrimEAA	− 0.0023	− 0.0073	0.0021	0.501	− 191.7	300
HbA_1c		− 0.0041	− 0.0087	4.0E-05	0.138	227.8	300
FEV1		0.0035	− 0.0018	0.0093	0.336	700.0	193
FVC		0.0050	0.0014	0.0096	0.026	− 138.9	193
FG	DNAm-based pack-years	− 0.0005	− 0.0068	0.0055	0.934	− 41.7	298
HbA_1c		− 0.0021	− 0.0074	0.0033	0.599	116.7	298
FEV1		− 0.0003	− 0.0076	0.0072	0.957	− 60.0	192
FVC		− 0.0028	− 0.0081	0.0029	0.501	77.8	192
FG	DNAm PAI-1	− 0.0009	− 0.0034	0.0005	0.443	− 75.0	300
HbA_1c		− 0.0015	− 0.0049	0.0007	0.345	83.3	300
FEV1		− 0.0004	− 0.0029	0.0017	0.767	− 80.0	193
FVC		0.0007	− 0.0006	0.0028	0.512	− 19.4	193
FG	DunedinPACE	− 0.0001	− 0.0015	0.0010	0.934	− 8.3	300
HbA_1c		− 0.0008	− 0.0030	0.0008	0.501	44.4	300
FEV1		0.0008	− 0.0009	0.0038	0.599	160.0	193
FVC		0.0014	− 0.0011	0.0048	0.467	− 38.9	193

^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 (years since smoking cessation) on Y (health outcome) through the mediator (EAA)
^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