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Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring
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posted on 2021-03-05, 07:39 authored by Josefine Jönsson, Kristina M. Renault, Sonia García-Calzón, Alexander Perfilyev, Angela C. Estampador, Kirsten Nørgaard, Mads Vendelbo Lind, Allan Vaag, Line Hjort, Kim F. Michaelsen, Emma Malchau Carlsen, Paul W. Franks, Charlotte LingMaternal 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.