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

Maguolo, Alice LU orcid ; Jönsson, Josefine LU orcid ; Perfilyev, Alexander LU orcid ; Maziarz, Marlena LU orcid ; Vaag, Allan LU ; Malchau Carlsen, Emma ; Nørgaard, Kirsten ; Franks, Paul W LU ; Renault, Kristina M and Ling, Charlotte LU orcid (2025) In Obesity 33(1). p.177-189
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... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, DNA Methylation, Female, Fetal Blood/metabolism, Body Mass Index, Pregnancy, Adult, Child, Preschool, Pediatric Obesity/genetics, Male, Obesity/genetics, Genome-Wide Association Study, CpG Islands, Epigenesis, Genetic, DNA-Binding Proteins/genetics
in
Obesity
volume
33
issue
1
pages
177 - 189
publisher
Nature Publishing Group
external identifiers
  • pmid:39663190
  • scopus:85211576019
ISSN
1930-739X
DOI
10.1002/oby.24174
language
English
LU publication?
yes
additional info
© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.
id
aa06c72d-6088-4c9e-ac03-514ee2b9a66c
date added to LUP
2025-01-10 11:26:50
date last changed
2025-05-31 15:26:00
@article{aa06c72d-6088-4c9e-ac03-514ee2b9a66c,
  abstract     = {{<p>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).</p><p>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).</p><p>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 &lt; 10%). Causal mediation analyses of 168 methylation sites associated with BMIz36 (p &lt; 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.</p><p>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.</p>}},
  author       = {{Maguolo, Alice and Jönsson, Josefine and Perfilyev, Alexander and Maziarz, Marlena and Vaag, Allan and Malchau Carlsen, Emma and Nørgaard, Kirsten and Franks, Paul W and Renault, Kristina M and Ling, Charlotte}},
  issn         = {{1930-739X}},
  keywords     = {{Humans; DNA Methylation; Female; Fetal Blood/metabolism; Body Mass Index; Pregnancy; Adult; Child, Preschool; Pediatric Obesity/genetics; Male; Obesity/genetics; Genome-Wide Association Study; CpG Islands; Epigenesis, Genetic; DNA-Binding Proteins/genetics}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{177--189}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Obesity}},
  title        = {{DNA methylation in cord blood partially mediates the effects of prepregnancy BMI on early childhood offspring BMI}},
  url          = {{http://dx.doi.org/10.1002/oby.24174}},
  doi          = {{10.1002/oby.24174}},
  volume       = {{33}},
  year         = {{2025}},
}