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The effect of paternal methyl-group donor intake on offspring DNA methylation and birth weight

  • S. Pauwels (a1) (a2), I. Truijen (a1), M. Ghosh (a1), R. C. Duca (a1), S. A. S. Langie (a2) (a3), B. Bekaert (a4) (a5), K. Freson (a6), I. Huybrechts (a7), G. Koppen (a2), R. Devlieger (a8) (a9) and L. Godderis (a1) (a10)...


Most nutritional studies on the development of children focus on mother–infant interactions. Maternal nutrition is critically involved in the growth and development of the fetus, but what about the father? The aim is to investigate the effects of paternal methyl-group donor intake (methionine, folate, betaine, choline) on paternal and offspring global DNA (hydroxy)methylation, offspring IGF2 DMR DNA methylation, and birth weight. Questionnaires, 7-day estimated dietary records, whole blood samples, and anthropometric measurements from 74 fathers were obtained. A total of 51 cord blood samples were collected and birth weight was obtained. DNA methylation status was measured using liquid chromatography-tandem mass spectrometry (global DNA (hydroxy)methylation) and pyrosequencing (IGF2 DMR methylation). Paternal betaine intake was positively associated with paternal global DNA hydroxymethylation (0.028% per 100 mg betaine increase, 95% CI: 0.003, 0.053, P=0.03) and cord blood global DNA methylation (0.679% per 100 mg betaine increase, 95% CI: 0.057, 1.302, P=0.03). Paternal methionine intake was positively associated with CpG1 (0.336% per 100 mg methionine increase, 95% CI: 0.103, 0.569, P=0.006), and mean CpG (0.201% per 100 mg methionine increase, 95% CI: 0.001, 0.402, P=0.049) methylation of the IGF2 DMR in cord blood. Further, a negative association between birth weight/birth weight-for-gestational age z-score and paternal betaine/methionine intake was found. In addition, a positive association between choline and birth weight/birth weight-for-gestational age z-score was also observed. Our data indicate a potential impact of paternal methyl-group donor intake on paternal global DNA hydroxymethylation, offspring global and IGF2 DMR DNA methylation, and prenatal growth.


Corresponding author

*Address for correspondence: S. Pauwels, Department of Public Health and Primary Care, Environment and Health, KU Leuven – University of Leuven, Kapucijnenvoer 35 blok D box 7001, 3000 Leuven, Belgium. (Email


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