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; Baiz, Nour; Hoyo, Cathrine; Agha, Golareh; Roy, Ritu; Holloway, John W.; Ghantous, Akram; Merid, Simon Kebede; Bakulski, Kelly M.; Kupers, Leanne K.; Zhang, Hongmei; Richmond, Rebecca C.; Page, Christian Magnus; Duijts, Liesbeth; Lie, Rolv T.; Melton, Phillip E.; Vonk, Judith M.; Nohr, Ellen Aagard; Williams-DeVane, ClarLynda; Huen, Karen; Rifas-Shiman, Sheryl L.; Ruiz Arenas, Carlos; Gonseth, Semira; Rezwan, Faisal I.; Herceg, Zdenko; Ekstrom, Sandra; Croen, Lisa; Falahi, Fahimeh; Perron, Patrice; Karagas, Margaret R.; Quraishi, Bilal M.; Suderman, Matthew; Magnus, Maria C.; Jaddoe, Vincent W.; Taylor, Jack A.; Anderson, Denise; Zhao, Shanshan; Smit, Henriette A.; Josey, Michele J.; Bradman, Asa; Baccarelli, Andrea A.; Bustamante Pineda, Mariona; Haberg, 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.; Sorensen, Thorkild I. A.; Koppelman, Gerard H.; Newnham, John P.; Wilcox, Allen J.; Nystad, Wenche; London, Stephanie J.; Felix, Janine F.; Relton, Caroline L.

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

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 associ...

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Autores:	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, Baiz, Nour, Hoyo, Cathrine, Agha, Golareh, Roy, Ritu, Holloway, John W., Ghantous, Akram, Merid, Simon Kebede, Bakulski, Kelly M., Kupers, Leanne K., Zhang, Hongmei, Richmond, Rebecca C., Page, Christian Magnus, Duijts, Liesbeth, Lie, Rolv T., Melton, Phillip E., Vonk, Judith M., Nohr, Ellen Aagard, Williams-DeVane, ClarLynda, Huen, Karen, Rifas-Shiman, Sheryl L., Ruiz Arenas, Carlos, Gonseth, Semira, Rezwan, Faisal I., Herceg, Zdenko, Ekstrom, Sandra, Croen, Lisa, Falahi, Fahimeh, Perron, Patrice, Karagas, Margaret R., Quraishi, Bilal M., Suderman, Matthew, Magnus, Maria C., Jaddoe, Vincent W., Taylor, Jack A., Anderson, Denise, Zhao, Shanshan, Smit, Henriette A., Josey, Michele J., Bradman, Asa, Baccarelli, Andrea A., Bustamante Pineda, Mariona, Haberg, 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., Sorensen, Thorkild I. A., Koppelman, Gerard H., Newnham, John P., Wilcox, Allen J., Nystad, Wenche, London, Stephanie J., Felix, Janine F., Relton, Caroline L.
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2017
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/117628
Acceso en línea:	https://hdl.handle.net/2445/117628
Access Level:	acceso abierto
Palabra clave:	Epigenètica Embaràs Epigenetics Pregnancy

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network_name_str	España
repository_id_str
dc.title.none.fl_str_mv	Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
title	Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
spellingShingle	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. Epigenètica Embaràs Epigenetics Pregnancy
title_short	Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
title_full	Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
title_fullStr	Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
title_full_unstemmed	Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
title_sort	Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
dc.creator.none.fl_str_mv	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 Baiz, Nour Hoyo, Cathrine Agha, Golareh Roy, Ritu Holloway, John W. Ghantous, Akram Merid, Simon Kebede Bakulski, Kelly M. Kupers, Leanne K. Zhang, Hongmei Richmond, Rebecca C. Page, Christian Magnus Duijts, Liesbeth Lie, Rolv T. Melton, Phillip E. Vonk, Judith M. Nohr, Ellen Aagard Williams-DeVane, ClarLynda Huen, Karen Rifas-Shiman, Sheryl L. Ruiz Arenas, Carlos Gonseth, Semira Rezwan, Faisal I. Herceg, Zdenko Ekstrom, Sandra Croen, Lisa Falahi, Fahimeh Perron, Patrice Karagas, Margaret R. Quraishi, Bilal M. Suderman, Matthew Magnus, Maria C. Jaddoe, Vincent W. Taylor, Jack A. Anderson, Denise Zhao, Shanshan Smit, Henriette A. Josey, Michele J. Bradman, Asa Baccarelli, Andrea A. Bustamante Pineda, Mariona Haberg, 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. Sorensen, Thorkild I. A. Koppelman, Gerard H. Newnham, John P. Wilcox, Allen J. Nystad, Wenche London, Stephanie J. Felix, Janine F. Relton, Caroline L.
author	Sharp, Gemma C.
author_facet	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 Baiz, Nour Hoyo, Cathrine Agha, Golareh Roy, Ritu Holloway, John W. Ghantous, Akram Merid, Simon Kebede Bakulski, Kelly M. Kupers, Leanne K. Zhang, Hongmei Richmond, Rebecca C. Page, Christian Magnus Duijts, Liesbeth Lie, Rolv T. Melton, Phillip E. Vonk, Judith M. Nohr, Ellen Aagard Williams-DeVane, ClarLynda Huen, Karen Rifas-Shiman, Sheryl L. Ruiz Arenas, Carlos Gonseth, Semira Rezwan, Faisal I. Herceg, Zdenko Ekstrom, Sandra Croen, Lisa Falahi, Fahimeh Perron, Patrice Karagas, Margaret R. Quraishi, Bilal M. Suderman, Matthew Magnus, Maria C. Jaddoe, Vincent W. Taylor, Jack A. Anderson, Denise Zhao, Shanshan Smit, Henriette A. Josey, Michele J. Bradman, Asa Baccarelli, Andrea A. Bustamante Pineda, Mariona Haberg, 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. Sorensen, Thorkild I. A. Koppelman, Gerard H. Newnham, John P. Wilcox, Allen J. Nystad, Wenche London, Stephanie J. Felix, Janine F. Relton, Caroline L.
author_role	author
author2	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 Baiz, Nour Hoyo, Cathrine Agha, Golareh Roy, Ritu Holloway, John W. Ghantous, Akram Merid, Simon Kebede Bakulski, Kelly M. Kupers, Leanne K. Zhang, Hongmei Richmond, Rebecca C. Page, Christian Magnus Duijts, Liesbeth Lie, Rolv T. Melton, Phillip E. Vonk, Judith M. Nohr, Ellen Aagard Williams-DeVane, ClarLynda Huen, Karen Rifas-Shiman, Sheryl L. Ruiz Arenas, Carlos Gonseth, Semira Rezwan, Faisal I. Herceg, Zdenko Ekstrom, Sandra Croen, Lisa Falahi, Fahimeh Perron, Patrice Karagas, Margaret R. Quraishi, Bilal M. Suderman, Matthew Magnus, Maria C. Jaddoe, Vincent W. Taylor, Jack A. Anderson, Denise Zhao, Shanshan Smit, Henriette A. Josey, Michele J. Bradman, Asa Baccarelli, Andrea A. Bustamante Pineda, Mariona Haberg, 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. Sorensen, Thorkild I. A. Koppelman, Gerard H. Newnham, John P. Wilcox, Allen J. Nystad, Wenche London, Stephanie J. Felix, Janine F. Relton, Caroline L.
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Epigenètica Embaràs Epigenetics Pregnancy
topic	Epigenètica Embaràs Epigenetics Pregnancy
description	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 x 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.
publishDate	2017
dc.date.none.fl_str_mv	2017 2017 2017 2017
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/117628
url	https://hdl.handle.net/2445/117628
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: http://dx.doi.org/10.1093/hmg/ddx290 Human Molecular Genetics, 2017, vol. 26, num. 20, p. 4067-4085 http://dx.doi.org/10.1093/hmg/ddx290 info:eu-repo/grantAgreement/EC/H2020/733206 info:eu-repo/grantAgreement/EC/H2020/648916 info:eu-repo/grantAgreement/EC/H2020/633595
dc.rights.none.fl_str_mv	cc by (c) Sharp et al., 2017 http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc by (c) Sharp et al., 2017 http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	19 p. application/pdf application/pdf
dc.publisher.none.fl_str_mv	Oxford University Press
publisher.none.fl_str_mv	Oxford University Press
dc.source.none.fl_str_mv	Articles publicats en revistes (ISGlobal) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling	Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortiumSharp, Gemma C.Salas, Lucas A.Monnereau, ClaireAllard, CatherineYousefi, PaulEverson, Todd M.Bohlin, JonXu, ZongliHuang, Rae-ChiReese, Sarah E.Xu, Cheng-JianBaiz, NourHoyo, CathrineAgha, GolarehRoy, RituHolloway, John W.Ghantous, AkramMerid, Simon KebedeBakulski, Kelly M.Kupers, Leanne K.Zhang, HongmeiRichmond, Rebecca C.Page, Christian MagnusDuijts, LiesbethLie, Rolv T.Melton, Phillip E.Vonk, Judith M.Nohr, Ellen AagardWilliams-DeVane, ClarLyndaHuen, KarenRifas-Shiman, Sheryl L.Ruiz Arenas, CarlosGonseth, SemiraRezwan, Faisal I.Herceg, ZdenkoEkstrom, SandraCroen, LisaFalahi, FahimehPerron, PatriceKaragas, Margaret R.Quraishi, Bilal M.Suderman, MatthewMagnus, Maria C.Jaddoe, Vincent W.Taylor, Jack A.Anderson, DeniseZhao, ShanshanSmit, Henriette A.Josey, Michele J.Bradman, AsaBaccarelli, Andrea A.Bustamante Pineda, MarionaHaberg, Siri E.Pershagen, GöranHertz-Picciotto, IrvaNewschaffer, CraigCorpeleijn, EvaBouchard, LuigiLawlor, Debbie A.Maguire, Rachel L.Barcellos, Lisa F.Davey Smith, GeorgeEskenazi, BrendaKarmaus, WilfriedMarsit, Carmen J.Hivert, Marie-FranceSnieder, HaroldFallin, M. DanieleMelén, ErikMunthe-Kaas, Monica C.Arshad, HasanWiemels, Joseph L.Annesi-Maesano, IsabellaVrijheid, MartineOken, EmilyHolland, NinaMurphy, Susan K.Sorensen, Thorkild I. A.Koppelman, Gerard H.Newnham, John P.Wilcox, Allen J.Nystad, WencheLondon, Stephanie J.Felix, Janine F.Relton, Caroline L.EpigenèticaEmbaràsEpigeneticsPregnancyPre-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 x 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.Oxford University Press2017201720172017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion19 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/117628Articles publicats en revistes (ISGlobal)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1093/hmg/ddx290Human Molecular Genetics, 2017, vol. 26, num. 20, p. 4067-4085http://dx.doi.org/10.1093/hmg/ddx290info:eu-repo/grantAgreement/EC/H2020/733206info:eu-repo/grantAgreement/EC/H2020/648916info:eu-repo/grantAgreement/EC/H2020/633595cc by (c) Sharp et al., 2017http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1176282026-05-29T05:05:01Z
score	15,811543

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

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