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Maternal dietary glycemic index and glycemic load in pregnancy and offspring cord blood DNA methylation

posted on 16.06.2022, 13:56 authored by Leanne K. Küpers, Sílvia Fernández-Barrés, Giulia Mancano, Laura Johnson, Raffael Ott, Jesus Vioque, Marco Colombo, Kathrin Landgraf, Elmar W. Tobi, Antje Körner, Romy Gaillard, Jeanne H.M. de Vries, Vincent W.V. Jaddoe, Martine Vrijheid, Gemma C. Sharp, Janine F. Felix


Objective: Suboptimal nutrition in pregnancy is associated with worse offspring cardiometabolic health. DNA methylation may be an underlying mechanism. We meta-analyzed epigenome-wide association studies (EWASs) of maternal dietary glycemic index and load with cord blood DNA methylation.

Research Design and Methods: We calculated maternal glycemic index and load from food frequency questionnaires, and ran EWASs on cord blood DNA methylation in 2003 mother-offspring pairs from three cohorts. Analyses were additionally stratified by maternal BMI categories. We looked-up the findings in EWASs of maternal glycemic traits and BMI, and in EWASs of birthweight and child BMI. We examined associations with gene expression in child blood in the online Human Early Life Exposome eQTM catalogue and in 223 adipose tissue samples.

Results: Maternal glycemic index and load were associated with cord blood DNA methylation at 41 cytosine-phosphate-guanine sites (CpGs, P<1.17x10-7), mostly in mothers with overweight/obesity. We did not observe overlap with CpGs associated with maternal glycemic traits, BMI or child birthweight or BMI. Only DNA methylation at cg24458009 and cg23347399 was associated with expression of PCED1B and PCDHG, respectively, in child blood, and DNA methylation at cg27193519 was associated with expression of TFAP4, ZNF500, PPL and ANKS3 in child subcutaneous adipose tissue. 

Conclusions: We observed multiple associations of maternal glycemic index and load during pregnancy with cord blood DNA methylation, mostly in mothers with overweight/obesity; some of these CpGs were associated with gene expression. Additional studies are required to further explore functionality, uncover causality, and study pathways to offspring health. 


This work was funded by the Joint Programming Initiative – A Healthy Diet for a Healthy Life (JPI HDHL) (NutriPROGRAM consortium and PREcisE consortium). Information regarding funding for the contributing cohorts and individual authors can be found in Supplemental File.