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Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation Which Associates With Body Composition in the Offspring

posted on 05.03.2021, 07:39 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 Ling
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.


Sygekassernes Helsefond, Brødrene Hartmann Fonden, Hvidovre Hospitals Forskningsfond and The Danish Council for Strategic Research supported the TOP-study. The work performed by A.C.E. and P.W.F. was supported by grants from the EFSD, Swedish Research Council, Swedish Heart Lung Foundation and the European Research Council (CoG-2015_681742_NASCENT) and Novo Nordisk Foundation. The work performed by J.J., S.G-C., A.P. and C.L. was supported by grants from the Novo Nordisk foundation, Swedish Research Council, Region Skåne (ALF), ERC-Co Grant (PAINTBOX, No 725840), H2020-Marie Skłodowska-Curie grant agreement No 706081 (EpiHope), Hjärt-Lungfonden, Exodiab, Swedish Foundation for Strategic Research for IRC15-0067 and Swedish Diabetes Foundation. All researchers from LUDC were supported by a research center grant from the Swedish Strategic Science Foundation.