Sex-specific role of epigenetic modification of a leptin upstream enhancer in adipose tissue

Clinical Epigenetics

Table 3 Causal mediation analysis of LEP UE methylation > LEP serum level > body fat percentage (in female individuals)

CpG site	a	b	c	ACME	ADE	Total effect	Prop. mediated
1	0.9296	0.29736***	0.9141**	0.2764**	0.6377**	0.9141***	0.3024**
2	0.5334	0.31914***	0.5347*	0.1702	0.3645**	0.5347**	0.3183
3	0.7282	0.30786***	0.6012**	0.2242	0.3770*	0.6012*	0.3729
4	1.327**	0.23764**	0.9708***	0.3155***	0.6554**	0.9708***	0.3249***
5	0.7471	0.29057***	0.7869***	0.2171	0.5698***	0.7869***	0.2759
6	1.0253*	0.26327***	0.9759***	0.2699*	0.7060***	0.9759***	0.2766*
Mean	1.0448*	0.2721***	0.9456***	0.2843**	0.6613**	0.9456***	0.3007**

Significance level: ***P < 0.001; **P < 0.01; *P < 0.05; and P < 0.1; regression coefficients: a—between LEP DNA methylation and LEP serum level in female individuals, b—between LEP serum level and body fat (corrected for DNA methylation effect), and c—direct effect between DNA methylation and body fat
ACME: average causal mediation effects = indirect effect of DNA methylation on body fat that goes through the mediator (LEP serum level), ADE: average direct effects = direct effect of DNA methylation on body fat when controlling for the mediator (LEP serum level), Total effect: direct + indirect effect of DNA methylation onto body fat (ACME + ADE), and Prop. mediated: proportion of DNA methylation on body fat that goes through the mediator (LEP serum level)

ISSN: 1868-7083