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Association between dietary patterns reflecting one-carbon metabolism nutrients intake before pregnancy and placental DNA methylation

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Version 2 2022-07-27, 10:40
Version 1 2021-08-31, 08:40
journal contribution
posted on 2022-07-27, 10:40 authored by Marion Lecorguillé, Marie-Aline Charles, Johanna Lepeule, Sandrine Lioret, Blandine de Lauzon-Guillain, Anne Forhan, Jörg Tost, Matthew Suderman, Barbara Heude

The preconception period represents an important window for foetal and epigenetic programming. Some micronutrients (B vitamins, choline, betaine, methionine) implicated in one-carbon metabolism (OCM) are essential for major epigenetic processes that take place in early pregnancy. However, few studies have evaluated the implication of the micronutrients in placental DNA methylation. We investigated whether intake of OCM nutrients in the year before pregnancy was associated with placental DNA methylation in the EDEN mother–child cohort. Maternal dietary intake was assessed with a food-frequency questionnaire. Three dietary patterns, ‘varied and balanced diet,’ ‘vegetarian tendency,’ and ‘bread and starchy food,’ were used to characterize maternal OCM dietary intake. The Illumina Infinium HumanMethylation450 BeadChip was used to measure placental DNA methylation of 573 women included in the analyses. We evaluated the association of dietary patterns with global DNA methylation. Then, we conducted an agnostic epigenome-wide association study (EWAS) and investigated differentially methylated regions (DMRs) associated with each dietary pattern. We found no significant association between the three dietary patterns and global DNA methylation or individual CpG sites. DMR analyses highlighted associations between the ‘varied and balanced’ or ‘vegetarian tendency’ pattern and DMRs located at genes previously implicated in functions essential for embryonic development, such as neurodevelopment. The ‘bread and starchy food’ pattern was associated with regions related to genes whose functions involve various metabolic and cell synthesis-related processes. In mainly well-nourished French women without major deficiencies, OCM intake before pregnancy was not associated with major variation in DNA methylation.


The EDEN study was supported by Foundation for Medical Research (FRM); National Agency for Research (ANR); National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program); French Ministry of Health (DGS); French Ministry of Research; INSERM Bone and Joint Diseases National Research (PRO-A); and Human Nutrition National Research Programs; Paris-Sud University; Nestlé; French National Institute for Population Health Surveillance (InVS); French National Institute for Health Education (INPES); the European Union FP7 programs (FP7/2007–2013, HELIX, ESCAPE, ENRIECO, Medall projects); Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients); French Agency for Environmental Health Safety (now ANSES); Mutuelle Générale de l’Education Nationale; a complementary health insurance; French national agency for food security; and French-speaking association for the study of diabetes and metabolism (ALFEDIAM). The placental DNA measurements were funded by the Fondation de France (grant 2012-00031617 - 2012-00031593) and the ANR (ANR-13-CESA-0011-05). The scientific mobility of M Lecorguillé into the MRC Integrative Epidemiology Unit for a 4-month research stay was possible in part because of funding from the ALPHABET project. This latter project was supported by an award from the European Union’s Horizon 2020 research and innovation program under the ERA-Net Cofund of the Joint Programming Initiative Healthy Diet for Healthy Life (JPI-HDHL) (http://www.healthydietforhealthylife.eu) (action no. 696295; Biomarkers for Nutrition and Health). M Lecorguillé received a doctoral mobility grant from the Public Health Doctoral Network from the EHESP (School for Higher Studies in Public Health) and the University of Paris Descartes. The funders had no role in the design and conduct of the study; in the management, analysis, and interpretation of the data; and preparation, review, or approval of the manu