Lifestyle intervention in pregnant women with obesity impacts cord blood DNA methylation which associates with body composition in the offspring
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Lifestyle intervention in pregnant women with obesity impacts cord blood DNA methylation which associates with body composition in the offspring. / Jönsson, Josefine; Renault, Kristina Martha; García-Calzón, Sonia; Perfilyev, Alexander; Estampador, Angela C; Nørgaard, Kirsten; Lind, Mads Vendelbo; Vaag, Allan; Hjort, Line; Michaelsen, Kim F.; Carlsen, Emma Malchau; Franks, Paul W; Ling, Charlotte.
In: Diabetes, Vol. 70, No. 4, 2021, p. 854-866.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Lifestyle intervention in pregnant women with obesity impacts cord blood DNA methylation which associates with body composition in the offspring
AU - Jönsson, Josefine
AU - Renault, Kristina Martha
AU - García-Calzón, Sonia
AU - Perfilyev, Alexander
AU - Estampador, Angela C
AU - Nørgaard, Kirsten
AU - Lind, Mads Vendelbo
AU - Vaag, Allan
AU - Hjort, Line
AU - Michaelsen, Kim F.
AU - Carlsen, Emma Malchau
AU - Franks, Paul W
AU - Ling, Charlotte
N1 - © 2021 by the American Diabetes Association.
PY - 2021
Y1 - 2021
N2 - Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (FDR<5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. DISC1, GBX2, HERC2 and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (p<0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring's lean mass and early growth.
AB - Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the TOP-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus controls (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus controls (FDR<5%) when using the Houseman reference-free method to correct for cell composition and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared to controls. Methylation at 17 sites, annotated to e.g. DISC1, GBX2, HERC2 and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR<5%). Moreover, 22 methylation sites were associated with offspring BMI z-scores during the first 3 years of life (p<0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring's lean mass and early growth.
U2 - 10.2337/db20-0487
DO - 10.2337/db20-0487
M3 - Journal article
C2 - 33431374
VL - 70
SP - 854
EP - 866
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 4
ER -
ID: 255165561