Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Leanne K. Küpers, Claire Monnereau, Gemma C. Sharp, Paul Yousefi, Lucas A. Salas, Akram Ghantous, Christian M. Page, Sarah E. Reese, Allen J. Wilcox, Darina Czamara, Anne P. Starling, Alexei Novoloaca, Samantha Lent, Ritu Roy, Cathrine Hoyo, Carrie V. Breton, Catherine Allard, Allan C. Just, Kelly M. Bakulski, John W. Holloway, Todd M. Everson, Cheng-Jian Xu, Rae-Chi Huang, Diana A. van der Plaat, Matthias Wielscher, Simon Kebede Merid, Vilhelmina Ullemar, Faisal I. Rezwan, Jari Lahti, Jenny van Dongen, Sabine A. S. Langie, Tom G. Richardson, Maria C. Magnus, Ellen A. Nohr, Zongli Xu, Liesbeth Duijts, Shanshan Zhao, Weiming Zhang, Michelle Plusquin, Dawn L. DeMeo, Olivia Solomon, Joosje H. Heimovaara, Dereje D. Jima, Lu Gao, Mariona Bustamante, Patrice Perron, Robert O. Wright, Irva Hertz-Picciotto, Hongmei Zhang, Margaret R. Karagas, Ulrike Gehring, Carmen J. Marsit, Lawrence J. Beilin, Judith M. Vonk, Marjo-Riitta Jarvelin, Anna Bergström, Anne K. Örtqvist, Susan Ewart, Pia M. Villa, Sophie E. Moore, Gonneke Willemsen, Arnout R. L. Standaert, Siri E. Håberg, Thorkild I. A. Sørensen, Jack A. Taylor, Katri Räikkönen, Ivana V. Yang, Katerina Kechris, Tim S. Nawrot, Matt J. Silver, Yun Yun Gong, Lorenzo Richiardi, Manolis Kogevinas, Augusto A. Litonjua, Brenda Eskenazi, Karen Huen, Hamdi Mbarek, Rachel L. Maguire, Terence Dwyer, Martine Vrijheid, Luigi Bouchard, Andrea A. Baccarelli, Lisa A. Croen, Wilfried Karmaus, Denise Anderson, Maaike de Vries, Sylvain Sebert, Juha Kere, Robert Karlsson, Syed Hasan Arshad, Esa Hämäläinen, Michael N. Routledge, Dorret I. Boomsma, Andrew P. Feinberg, Craig J. Newschaffer, Eva Govarts, Matthieu Moisse, M. Daniele Fallin, Erik Melén, Andrew M. Prentice, Eero Kajantie, Catarina Almqvist, Emily Oken, Dana Dabelea, H. Marike Boezen, Phillip E. Melton, Rosalind J. Wright, Gerard H. Koppelman, Letizia Trevisi, Marie-France Hivert, Jordi Sunyer, Monica C. Munthe-Kaas, Susan K. Murphy, Eva Corpeleijn, Joseph Wiemels, Nina Holland, Zdenko Herceg, Elisabeth B. Binder, George Davey Smith, Vincent W. V. Jaddoe, Rolv T. Lie, Wenche Nystad, Stephanie J. London, Debbie A. Lawlor (), Caroline L. Relton (), Harold Snieder () and Janine F. Felix ()
Additional contact information
Leanne K. Küpers: University of Bristol
Claire Monnereau: University Medical Center Rotterdam
Gemma C. Sharp: University of Bristol
Paul Yousefi: University of Bristol
Lucas A. Salas: Geisel School of Medicine at Dartmouth College
Akram Ghantous: Epigenetics Group, International Agency for Research on Cancer
Christian M. Page: Norwegian Institute of Public Health
Sarah E. Reese: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Service, Research Triangle Park
Allen J. Wilcox: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Service, Research Triangle Park
Darina Czamara: Max-Planck-Institute of Psychiatry
Anne P. Starling: University of Colorado Anschutz Medical Campus
Alexei Novoloaca: Epigenetics Group, International Agency for Research on Cancer
Samantha Lent: Boston University School of Public Health
Ritu Roy: University of California
Cathrine Hoyo: North Carolina State University
Carrie V. Breton: University of Southern California
Catherine Allard: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Allan C. Just: Icahn School of Medicine at Mount Sinai
Kelly M. Bakulski: University of Michigan
John W. Holloway: University of Southampton
Todd M. Everson: Rollins School of Public Health at Emory University
Cheng-Jian Xu: University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, Groningen Research Institute for Asthma and COPD
Rae-Chi Huang: University of Western Australia
Diana A. van der Plaat: University Medical Center Groningen, Department of Epidemiology and Groningen Research Institute for Asthma and COPD (GRIAC)
Matthias Wielscher: School of Public Health, Imperial College London
Simon Kebede Merid: Institute of Environmental Medicine, Karolinska Institutet
Vilhelmina Ullemar: Karolinska Institutet
Faisal I. Rezwan: University of Southampton, Southampton General Hospital
Jari Lahti: University of Helsinki
Jenny van Dongen: Vrije Universiteit Amsterdam
Sabine A. S. Langie: VITO - Health
Tom G. Richardson: University of Bristol
Maria C. Magnus: University of Bristol
Ellen A. Nohr: University of Southern Denmark
Zongli Xu: University Medical Center Rotterdam
Liesbeth Duijts: Wageningen University
Shanshan Zhao: National Institute of Environmental Health Sciences, NIH, Research Triangle Park
Weiming Zhang: University of Colorado Anschutz Medical Campus
Michelle Plusquin: Hasselt University
Dawn L. DeMeo: Brigham and Women’s Hospital, Harvard Medical School
Olivia Solomon: University of Bristol
Joosje H. Heimovaara: University Medical Center Groningen, Department of Epidemiology
Dereje D. Jima: North Carolina State University
Lu Gao: University of Southern California
Mariona Bustamante: ISGlobal, Bacelona Institute for Global Health
Patrice Perron: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Robert O. Wright: Icahn School of Medicine at Mount Sinai
Irva Hertz-Picciotto: University of California Davis MIND Institute
Hongmei Zhang: University of Memphis
Margaret R. Karagas: Geisel School of Medicine at Dartmouth College
Ulrike Gehring: Utrecht University
Carmen J. Marsit: Rollins School of Public Health at Emory University
Lawrence J. Beilin: University of Western Australia
Judith M. Vonk: University Medical Center Groningen, Department of Epidemiology and Groningen Research Institute for Asthma and COPD (GRIAC)
Marjo-Riitta Jarvelin: School of Public Health, Imperial College London
Anna Bergström: Institute of Environmental Medicine, Karolinska Institutet
Anne K. Örtqvist: Karolinska Institutet
Susan Ewart: Michigan State University
Pia M. Villa: University of Helsinki and Helsinki University Hospital
Sophie E. Moore: Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine
Gonneke Willemsen: Vrije Universiteit Amsterdam
Arnout R. L. Standaert: VITO - Health
Siri E. Håberg: Norwegian Institute of Public Health
Thorkild I. A. Sørensen: University of Bristol
Jack A. Taylor: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Service, Research Triangle Park
Katri Räikkönen: University of Helsinki
Ivana V. Yang: University of Colorado Anschutz Medical Campus
Katerina Kechris: University Medical Center Rotterdam
Tim S. Nawrot: Hasselt University
Matt J. Silver: Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine
Yun Yun Gong: University of Leeds
Lorenzo Richiardi: University of Turin
Manolis Kogevinas: ISGlobal, Bacelona Institute for Global Health
Augusto A. Litonjua: Brigham and Women’s Hospital, Harvard Medical School
Brenda Eskenazi: University of California
Karen Huen: University of California
Hamdi Mbarek: Vrije Universiteit Amsterdam
Rachel L. Maguire: North Carolina State University
Terence Dwyer: University of Oxford
Martine Vrijheid: ISGlobal, Bacelona Institute for Global Health
Luigi Bouchard: Université de Sherbrooke
Andrea A. Baccarelli: Columbia University Mailman School of Public Health
Lisa A. Croen: Division of Research, Kaiser Permanente Northern California
Wilfried Karmaus: University of Memphis
Denise Anderson: University of Western Australia
Maaike de Vries: University Medical Center Groningen, Department of Epidemiology and Groningen Research Institute for Asthma and COPD (GRIAC)
Sylvain Sebert: University of Oulu
Juha Kere: University of Helsinki
Robert Karlsson: Karolinska Institutet
Syed Hasan Arshad: University of Southampton
Esa Hämäläinen: University of Helsinki
Michael N. Routledge: LICAMM, School of Medicine, Univeristy of Leeds
Dorret I. Boomsma: Vrije Universiteit Amsterdam
Andrew P. Feinberg: Johns Hopkins University School of Medicine
Craig J. Newschaffer: Drexel University
Eva Govarts: VITO - Health
Matthieu Moisse: KU Leuven – University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Institute for Neuroscience and Disease (LIND)
M. Daniele Fallin: Johns Hopkins University
Erik Melén: Institute of Environmental Medicine, Karolinska Institutet
Andrew M. Prentice: Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine
Eero Kajantie: National Institute for Health and Welfare, Helsinki and Oulu
Catarina Almqvist: Karolinska Institutet
Emily Oken: Harvard Pilgrim Health Care Institute
Dana Dabelea: University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus
H. Marike Boezen: University Medical Center Groningen, Department of Epidemiology and Groningen Research Institute for Asthma and COPD (GRIAC)
Phillip E. Melton: University of Western Australia
Rosalind J. Wright: Icahn School of Medicine at Mount Sinai
Gerard H. Koppelman: University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, Groningen Research Institute for Asthma and COPD
Letizia Trevisi: Harvard Medical School
Marie-France Hivert: Universite de Sherbrooke
Jordi Sunyer: ISGlobal, Bacelona Institute for Global Health
Monica C. Munthe-Kaas: Norwegian Institute of Public Health
Susan K. Murphy: Duke University Medical Center
Eva Corpeleijn: University Medical Center Groningen, Department of Epidemiology
Joseph Wiemels: University of California
Nina Holland: University of California
Zdenko Herceg: Epigenetics Group, International Agency for Research on Cancer
Elisabeth B. Binder: Max-Planck-Institute of Psychiatry
George Davey Smith: University of Bristol
Vincent W. V. Jaddoe: University Medical Center Rotterdam
Rolv T. Lie: Norwegian Institute of Public Health
Wenche Nystad: Norwegian Institute for Public Health
Stephanie J. London: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Service, Research Triangle Park
Debbie A. Lawlor: University of Bristol
Caroline L. Relton: University of Bristol
Harold Snieder: University Medical Center Groningen, Department of Epidemiology
Janine F. Felix: University Medical Center Rotterdam

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni

Date: 2019
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DOI: 10.1038/s41467-019-09671-3

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