A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation
Giulietta S. Monasso,
Thanh T. Hoang,
Giulia Mancano,
Sílvia Fernández-Barrés,
John Dou,
Vincent W.V. Jaddoe,
Christian M. Page,
Laura Johnson,
Mariona Bustamante,
Kelly M. Bakulski,
Siri E. Håberg,
Per M. Ueland,
Thomas Battram,
Simon K. Merid,
Erik Melén,
Doretta Caramaschi,
Leanne K. Küpers,
Jordi Sunyer,
Wenche Nystad,
Sandra G. Heil,
Rebecca J. Schmidt,
Martine Vrijheid,
Gemma C. Sharp,
Stephanie J. London,
Janine F. Felix
Affiliations
Giulietta S. Monasso
University Medical Center Rotterdam
Thanh T. Hoang
Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park
Giulia Mancano
University of Bristol
Sílvia Fernández-Barrés
ISGlobal, Bacelona Institute for Global Health
John Dou
University of Michigan
Vincent W.V. Jaddoe
University Medical Center Rotterdam
Christian M. Page
Norwegian Institute of Public Health
Laura Johnson
University of Bristol
Mariona Bustamante
ISGlobal, Bacelona Institute for Global Health
Kelly M. Bakulski
University of Michigan
Siri E. Håberg
Norwegian Institute of Public Health
Per M. Ueland
BEVITAL
Thomas Battram
University of Bristol
Simon K. Merid
Institute of Environmental Medicine, Karolinska Institutet
Erik Melén
Institute of Environmental Medicine, Karolinska Institutet
Doretta Caramaschi
University of Exeter
Leanne K. Küpers
University Medical Center Rotterdam
Jordi Sunyer
ISGlobal, Bacelona Institute for Global Health
Wenche Nystad
Norwegian Institute of Public Health
Sandra G. Heil
University Medical Center Rotterdam
Rebecca J. Schmidt
University of California Davis
Martine Vrijheid
ISGlobal, Bacelona Institute for Global Health
Gemma C. Sharp
University of Bristol
Stephanie J. London
Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park
Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or cord blood (n = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4–10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood (PFDR<0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.
