DNA methylation mediates the effect of maternal smoking on offspring birthweight: a birth cohort study of multi-ethnic US mother–newborn pairs

Table 3 Mediation effect of single CpG, single gene score, and combined mediation effect of the GFI1, AHRR, and CYP1A1 genes on the maternal smoking-newborn birthweight association in 954 mother–newborn pairs from the Boston Birth Cohort

Gene/CpG	Mediated effect (VanderWeele-Vansteelandt Approach)
Gene/CpG	Beta	SE	P	% Mediated
GFI1 gene score	− 70.1	24.0	0.004	44.6
AHRR CpG cg05575921	− 61.7	28.3	0.029	38.5
CYP1A1 gene score*	− 47.9	15.5	0.002	29.8

Model parameters	Mediation effect by structural equation model (simultaneous consideration of the 3 genes)
Model parameters	Beta	SE	P
Direct effect of maternal smoking	− 50.4	42.8	0.239
Indirect effect via GFI1 gene score	− 31.3	11.6	0.007
Indirect effect via AHRR CpG cg05575921	− 55.2	13.3	< 0.001
Indirect effect via CYP1A1 gene score	− 18.6	8.5	0.022
Sum of indirect effect (or mediation effect)	− 106.0	18.3	< 0.001
Total effect of maternal smoking	− 156.4	40.7	< 0.001
Percent mediated	67.8%

All models adjusted for maternal age, education level, race, parity, pre-pregnancy BMI, alcohol consumption, pre-gestational/gestational diabetes, gestational age, child sex, cord blood cell compositions (CD8, CD4, NK, B cell, monocytes, granulocytes, nucleated red blood cells)

ISSN: 1868-7083