Abstract
Objective: 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). Methods: 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). Results: 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. Conclusions: CB DNAm at birth may partially mediate effects of prePregBMI on early childhood BMIz36, supporting its plausible role in influencing individual future obesity risk.
| Original language | English |
|---|---|
| Journal | Obesity |
| Volume | 33 |
| Issue number | 1 |
| Pages (from-to) | 177-189 |
| ISSN | 1930-7381 |
| DOIs | |
| Publication status | Published - 2025 |
Bibliographical note
Funding Information:Sygekassernes Helsefond, Br\u00F8drene Hartmann Fonden, Hvidovre Hospitals Forskningsfond, and the Danish Council for Strategic Research supported the Treatment of Obese Pregnant Women (TOP) study. The work performed by Paul W. Franks was supported by grants from the European Foundation for the Study of Diabetes (EFSD), the Swedish Research Council, Hj\u00E4rt\u2010Lungfonden, the European Research Council (CoG\u20102015_681742_NASCENT), and the Novo Nordisk Foundation. The work performed by Josefine J\u00F6nsson, Alexander Perfilyev, and Charlotte Ling was supported by grants from the Novo Nordisk Foundation, the Swedish Research Council (Dnr 2018\u201002567 and 2021\u201000628), Region Sk\u00E5ne (ALF), Hj\u00E4rt\u2010Lungfonden, Strategic Research Area Exodiab (Dnr 2009\u20101039), the Swedish Foundation for Strategic Research (IRC15\u20100067), and the Swedish Diabetes Foundation. A research center grant from the Swedish Foundation of Strategic Research (EXODIAB) supported all researchers from the Lund University Diabetes Centre (LUDC). The work by Alice Maguolo was supported by Fondo Gianesini Emma and the work by Alice Maguolo and Charlotte Ling was supported by Obelisk European Union's Horizon Europe Research and Innovation program (101080465).
Publisher Copyright:
© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.