DNA methylation in cord blood partially mediates the effects of prepregnancy BMI on early childhood offspring BMI.

Autor: Maguolo A; 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., Jönsson J; Epigenetics and Diabetes Unit, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden., Perfilyev A; Epigenetics and Diabetes Unit, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden., Maziarz M; Bioinformatics Unit, Department of Clinical Sciences Malmö, Lund University Diabetes Center, Malmö, Sweden., Vaag A; Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden.; Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark., Malchau Carlsen E; Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark.; Department of Neonatology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Nørgaard K; Copenhagen University Hospital, Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Franks PW; Department of Clinical Science, Lund University, Helsingborg Hospital, Helsingborg, Sweden.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Renault KM; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Gynecology, Fertility and Obstetrics, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Ling C; Epigenetics and Diabetes Unit, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden.
Jazyk: angličtina
Zdroj: Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2025 Jan; Vol. 33 (1), pp. 177-189. Date of Electronic Publication: 2024 Dec 11.
DOI: 10.1002/oby.24174
Abstrakt: 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.
(© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)
Databáze: MEDLINE
Externí odkaz: