Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

Gemma C Sharp*, Paul Yousefi, Leanne Kupers, George Davey Smith, Deborah A Lawlor, Thorkild I. A. Sørensen, Caroline L Relton, et al.

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
74 Downloads (Pure)


Background: Accumulating evidence links paternal adiposity in the peri-conceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans.
Methods: In the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of co-ordinated epigenome-wide association studies (EWAS) of paternal prenatal Body Mass Index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 datasets; total n= 4,894) and in childhood (six datasets; total n = 1,982).
Results: We found little evidence of association at either time point: for all CpGs, the False Discovery Rate-adjusted P-values were >0.05. In secondary sex-stratified analyses, we found just four CpGs where there was robust evidence of association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes.
Conclusion: Our findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring blood DNA methylation, even at imprinted regions.
Original languageEnglish
Article numberdyaa267
Pages (from-to)1297-1315
Number of pages19
JournalInternational Journal of Epidemiology
Issue number4
Early online date29 Jan 2021
Publication statusPublished - 30 Aug 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.


  • paternal
  • fathers
  • body mass index
  • DNA methylation
  • epigenetics
  • DOHaD
  • pregnancy


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