Maguolo Alice, Jönsson Josefine, Perfilyev Alexander, Maziarz Marlena, Vaag Allan, Malchau Carlsen Emma, Nørgaard Kirsten, Franks Paul W, Renault Kristina M, Ling Charlotte
Epigenetics and Diabetes Unit, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden.
Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Pediatrics, and Gynecology, University of Verona, Verona, Italy.
Obesity (Silver Spring). 2025 Jan;33(1):177-189. doi: 10.1002/oby.24174. Epub 2024 Dec 11.
We investigated whether prepregnancy BMI (prePregBMI) in women with obesity was associated with differential DNA methylation (DNAm) in cord blood (CB) and whether DNAm may mediate the association of prePregBMI and early childhood BMI z score (BMIz).
From the Treatment of Obese Pregnant Women (TOP) study, 232 mother-child pairs were included. We conducted an epigenome-wide association study on prePregBMI and CB DNAm (450k array), followed by causal mediation analyses to test whether DNAm may mediate effects of prePregBMI on BMIz at age 36 months (BMIz36).
DNAm at 5345 CpG sites annotated to 2842 genes, which were overrepresented in biological processes linked to carbohydrate metabolism and plasma lipoprotein particle clearance, was associated with prePregBMI (false discovery rate < 10%). Causal mediation analyses of 168 methylation sites associated with BMIz36 (p < 0.05) and overlapping with the 5345 prePregBMI-associated sites identified two sites on SYT7 and DEAF1, partially mediating the effect of prePregBMI on BMIz36 (p ≤ 0.01). After cross-validation, a methylation risk score including these two sites could predict the highest quartile of BMIz36 and fat mass (in grams) with area under the curve = 0.72 (95% CI: 0.58-0.85) and area under the curve = 0.71 (95% CI: 0.58-0.85), respectively.
CB DNAm at birth may partially mediate effects of prePregBMI on early childhood BMIz36, supporting its plausible role in influencing individual future obesity risk.
我们研究了肥胖女性的孕前体重指数（prePregBMI）是否与脐带血（CB）中的差异DNA甲基化（DNAm）相关，以及DNAm是否可能介导prePregBMI与幼儿BMI z评分（BMIz）之间的关联。
纳入了来自肥胖孕妇治疗（TOP）研究的232对母婴。我们对prePregBMI和CB DNAm（450k芯片）进行了全表观基因组关联研究，随后进行因果中介分析，以检验DNAm是否可能介导prePregBMI对36个月龄时BMIz（BMIz36）的影响。
注释到2842个基因的5345个CpG位点的DNAm与prePregBMI相关（错误发现率<10%），这些基因在与碳水化合物代谢和血浆脂蛋白颗粒清除相关的生物学过程中过度富集。对与BMIz36相关（p<0.05）且与5345个prePregBMI相关位点重叠的168个甲基化位点进行的因果中介分析确定了SYT7和DEAF1上的两个位点，部分介导了prePregBMI对BMIz36的影响（p≤0.01）。经过交叉验证，包含这两个位点的甲基化风险评分可以分别预测BMIz36和脂肪量（以克为单位）的最高四分位数，曲线下面积分别为0.72（95%CI：0.58-0.85）和0.71（95%CI：0.58-0.85）。
出生时的CB DNAm可能部分介导prePregBMI对幼儿BMIz36的影响，支持其在影响个体未来肥胖风险方面的合理作用。
