Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
Human molecular genetics, v 26(20), pp 4067-4085
15 Oct 2017
PMID: 29016858
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
Metrics
Details
- Title
- Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
- Creators
- Gemma C Sharp - University of BristolLucas A Salas - Dartmouth CollegeClaire Monnereau - Erasmus University RotterdamCatherine Allard - Université de SherbrookePaul Yousefi - University of California, BerkeleyTodd M Everson - Emory UniversityJon Bohlin - Norwegian Institute of Public HealthZongli Xu - National Institutes of HealthRae-Chi Huang - University of Western AustraliaSarah E Reese - National Institutes of HealthCheng-Jian Xu - University Medical Center GroningenNour Baïz - University of ParisCathrine Hoyo - North Carolina State UniversityGolareh Agha - Columbia UniversityRitu Roy - University of California, San FranciscoJohn W Holloway - University of SouthamptonAkram Ghantous - International Agency For Research On CancerSimon K Merid - Karolinska InstituteKelly M Bakulski - University of Michigan–Ann ArborLeanne K Küpers - Medical Research CouncilHongmei Zhang - University of MemphisRebecca C Richmond - Medical Research CouncilChristian M Page - Norwegian Institute of Public HealthLiesbeth Duijts - Erasmus University RotterdamRolv T Lie - Norwegian Institute of Public HealthPhillip E Melton - University of Western AustraliaJudith M Vonk - University Medical Center GroningenEllen A Nohr - University of Southern DenmarkClarLynda Williams-DeVane - North Carolina Central UniversityKaren Huen - University of California, BerkeleySheryl L Rifas-Shiman - Harvard UniversityCarlos Ruiz-Arenas - Pompeu Fabra UniversitySemira Gonseth - University of California, BerkeleyFaisal I Rezwan - University of SouthamptonZdenko Herceg - International Agency For Research On CancerSandra Ekström - Karolinska InstituteLisa Croen - Kaiser PermanenteFahimeh Falahi - University Medical Center GroningenPatrice Perron - Université de SherbrookeMargaret R Karagas - Dartmouth CollegeBilal M Quraishi - University of MemphisMatthew Suderman - Medical Research CouncilMaria C Magnus - Medical Research CouncilVincent W V Jaddoe - Erasmus University RotterdamJack A Taylor - United States Department of Health and Human ServicesDenise Anderson - University of Western AustraliaShanshan Zhao - National Institutes of HealthHenriette A Smit - Utrecht UniversityMichele J Josey - North Carolina Central UniversityAsa Bradman - University of California, BerkeleyAndrea A Baccarelli - Columbia UniversityMariona Bustamante - Pompeu Fabra UniversitySiri E Håberg - Norwegian Institute of Public HealthGöran Pershagen - Karolinska InstituteIrva Hertz-Picciotto - University of California, DavisCraig Newschaffer - Drexel UniversityEva Corpeleijn - University Medical Center GroningenLuigi Bouchard - Université de SherbrookeDebbie A Lawlor - Medical Research CouncilRachel L Maguire - Duke UniversityLisa F Barcellos - University of California, BerkeleyGeorge Davey Smith - School of Social and Community MedicineBrenda Eskenazi - University of California, BerkeleyWilfried Karmaus - University Medical Center GroningenCarmen J Marsit - Emory UniversityMarie-France Hivert - Université de SherbrookeHarold Snieder - University Medical Center GroningenM Daniele Fallin - Johns Hopkins UniversityErik Melén - Karolinska InstituteMonica C Munthe-Kaas - Oslo University HospitalHasan Arshad - The David Hide Asthma and Allergy Research Centre, Isle of Wight, UKJoseph L Wiemels - University of California, San FranciscoIsabella Annesi-Maesano - University of ParisMartine Vrijheid - Pompeu Fabra UniversityEmily Oken - Harvard UniversityNina Holland - University of California, BerkeleySusan K Murphy - Duke UniversityThorkild I A Sørensen - Medical Research CouncilGerard H Koppelman - University Medical Center GroningenJohn P Newnham - University of Western AustraliaAllen J Wilcox - National Institutes of HealthWenche Nystad - Norwegian Institute of Public HealthStephanie J London - National Institutes of HealthJanine F Felix - Erasmus University RotterdamCaroline L Relton - Medical Research Council
- Publication Details
- Human molecular genetics, v 26(20), pp 4067-4085
- Publisher
- Oxford University Press
- Grant note
- R01 MH094609 / NIMH NIH HHS K12 HD043446 / NICHD NIH HHS MC_UU_12013/5 / Medical Research Council MC_UU_12013/1 / Medical Research Council R01 AI121226 / NIAID NIH HHS R01 ES021369 / NIEHS NIH HHS P01 ES022832 / NIEHS NIH HHS MC_UU_12013/2 / Medical Research Council P50 ES018172 / NIEHS NIH HHS MC_PC_15018 / Medical Research Council R01 DK103246 / NIDDK NIH HHS R25 CA134286 / NCI NIH HHS G9815508 / Medical Research Council R24 ES028507 / NIEHS NIH HHS P01 ES018172 / NIEHS NIH HHS R01 ES022223 / NIEHS NIH HHS R01 ES025531 / NIEHS NIH HHS 648916 / European Research Council P20 GM104416 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000412427100016
- Scopus ID
- 2-s2.0-85031735831
- Other Identifier
- 991019231755204721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Genetics & Heredity