Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium.

Sharp, Gemma C

Salas, Lucas A

Monnereau, Claire

Allard, Catherine

Yousefi, Paul

Everson, Todd M

Bohlin, Jon

Xu, Zongli

Huang, Rae-Chi

Reese, Sarah E

Xu, Cheng-Jian

Baïz, Nour

Hoyo, Cathrine

Agha, Golareh

Roy, Ritu

Holloway, John W

Ghantous, Akram

Merid, Simon K

Bakulski, Kelly M

Küpers, Leanne K

Zhang, Hongmei

Richmond, Rebecca C

Page, Christian M

Duijts, Liesbeth

Lie, Rolv T

Melton, Phillip E

Vonk, Judith M

Nohr, Ellen A

Williams-DeVane, ClarLynda

Huen, Karen

Rifas-Shiman, Sheryl L

Ruiz-Arenas, Carlos

Gonseth, Semira

Rezwan, Faisal I

Herceg, Zdenko

Ekström, Sandra

Croen, Lisa

Falahi, Fahimeh

Perron, Patrice

Karagas, Margaret R

Quraishi, Bilal M

Suderman, Matthew

Magnus, Maria C

Jaddoe, Vincent WV

Taylor, Jack A

Anderson, Denise

Zhao, Shanshan

Smit, Henriette A

Josey, Michele J

Bradman, Asa

Baccarelli, Andrea A

Bustamante, Mariona

Håberg, Siri E

Pershagen, Göran

Hertz-Picciotto, Irva

Newschaffer, Craig

Corpeleijn, Eva

Bouchard, Luigi

Lawlor, Debbie A

Maguire, Rachel L

Barcellos, Lisa F

Davey Smith, George

Eskenazi, Brenda

Karmaus, Wilfried

Marsit, Carmen J

Hivert, Marie-France

Snieder, Harold

Fallin, M Daniele

Melén, Erik

Munthe-Kaas, Monica C

Arshad, Hasan

Wiemels, Joseph L

Annesi-Maesano, Isabella

Vrijheid, Martine

Oken, Emily

Holland, Nina

Murphy, Susan K

Sørensen, Thorkild IA

Koppelman, Gerard H

Newnham, John P

Wilcox, Allen J

Nystad, Wenche

London, Stephanie J

Felix, Janine F

Relton, Caroline L

England

2017-11-01T13:54:37Z

2017-11-01T13:54:37Z

2017-10-15

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.

https://www.ncbi.nlm.nih.gov/pubmed/29016858

3988352

1460-2083

https://hdl.handle.net/10161/15695

eng

Oxford University Press (OUP)

Hum Mol Genet

10.1093/hmg/ddx290

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium.

Journal article

Williams-DeVane, ClarLynda|0000-0002-1013-5545

Murphy, Susan K|0000-0001-8298-7272

https://www.ncbi.nlm.nih.gov/pubmed/29016858

4067

4085

20

Clinical Science Departments

Duke

Duke Cancer Institute

Environmental Sciences and Policy

Institutes and Centers

Nicholas School of the Environment

Obstetrics and Gynecology

Obstetrics and Gynecology, Gynecologic Oncology

Pathology

School of Medicine

Published

26