Mediation effect of DNA methylation in associations between birth weight and adulthood obesity in women in China / 中华流行病学杂志

ABSTRACT

Objective@#To evaluate the possible mediation effect of DNA methylation in the associations between birth weight and adulthood obesity in women in China.@*Methods@#A cross-sectional survey was conducted in 1 602 women with genetic relationship in urban area of Shanghai during March-December 2016. Information about their birth weight, birth length, current lifestyle and disease history were collected and body measurement was conducted at the interview. DNA methylation at specific sites of GNASAS, IGF2, IGF2-R, IL10 and LEP were measured using bisulphite pyrosequencing. Generalized estimating equations models with restricted cubic spline functions were used to estimate the associations of birth weight with BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-hip ratio (WHtR) in adulthood, and their associations with DNA methylation were evaluated using multilevel linear models. Multilevel structural equation models were used to evaluate the mediation effect of DNA methylation.@*Results@#A significant non-linear association was observed between birth weight and WC as well as WHtR (P<0.05). Lower birth weight was associated with higher level of methylation at IGF2-DMR (CpG1, 2), IGF2-R (CpG8, 10, 13, 16 and 17), with β coefficients and 95%CI being -4.35 (-7.30- -1.39), -4.50 (-7.59- -1.41), -2.33 (-4.60- -0.05), -1.78 (-3.88- -0.33), -2.58 (-4.82- -0.34), -2.03 (-4.00- -0.06) and -1.87 (-3.73- -0.01), respectively, but related with a lower level of methylation at LEP CpG16 (β=4.19, 95%CI 0.37- 8.00). Lower level of methylation at IGF2-DMR (CpG7), IGF2-R (CpG3, 5, 8, 9, 10, 14, 17, 19) and LEP (CpG3, 8, 10) was associated with larger WC, with β coefficients ranging from -0.016 to -0.040 (all P<0.05). Methylation at IGF2-R CpG8 was observed to mediate the association of birth weight and WC, and could explain 3.3% of the association.@*Conclusion@#Our results suggested that DNA methylation might mediate the effect of nutrition in uteri on adulthood central obesity in women in China.