Publication

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

Sharp, G. C., Salas, L. A., Monnereau, C., Allard, C., Yousefi, P., Everson, T. M., Bohlin, J., Xu, Z., Huang, R-C., Reese, S. E., Xu, C-J., Baïz, N., Hoyo, C., Agha, G., Roy, R., Holloway, J. W., Ghantous, A., Merid, S. K., Bakulski, K. M., Küpers, L. K., Zhang, H., Richmond, R. C., Page, C. M., Duijts, L., Lie, R. T., Melton, P. E., Vonk, J. M., Nohr, E. A., Williams-DeVane, C., Huen, K., Rifas-Shiman, S. L., Ruiz-Arenas, C., Gonseth, S., Rezwan, F. I., Herceg, Z., Ekström, S., Croen, L., Falahi, F., Perron, P., Karagas, M. R., Quraishi, B. M., Suderman, M., Magnus, M. C., Jaddoe, V. W. V., Taylor, J. A., Anderson, D., Zhao, S., Smit, H. A., Josey, M. J., Bradman, A., Baccarelli, A. A., Bustamante, M., Håberg, S. E., Pershagen, G., Hertz-Picciotto, I., Newschaffer, C., Corpeleijn, E., Bouchard, L., Lawlor, D. A., Maguire, R. L., Barcellos, L. F., Davey Smith, G., Eskenazi, B., Karmaus, W., Marsit, C. J., Hivert, M-F., Snieder, H., Fallin, M. D., Melén, E., Munthe-Kaas, M. C., Arshad, H., Wiemels, J. L., Annesi-Maesano, I., Vrijheid, M., Oken, E., Holland, N., Murphy, S. K., Sørensen, T. I. A., Koppelman, G. H., Newnham, J. P., Wilcox, A. J., Nystad, W., London, S. J., Felix, J. F. & Relton, C. L. 15-Oct-2017 In : Human Molecular Genetics. 26, 20, p. 4067-4085 19 p.

Research output: Contribution to journalArticle

APA

Sharp, G. C., Salas, L. A., Monnereau, C., Allard, C., Yousefi, P., Everson, T. M., ... Relton, C. L. (2017). 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, 26(20), 4067-4085. DOI: 10.1093/hmg/ddx290

Author

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 W V ; 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 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. In: Human Molecular Genetics. 2017 ; Vol. 26, No. 20. pp. 4067-4085

Harvard

Sharp, GC, Salas, LA, Monnereau, C, Allard, C, Yousefi, P, Everson, TM, Bohlin, J, Xu, Z, Huang, R-C, Reese, SE, Xu, C-J, Baïz, N, Hoyo, C, Agha, G, Roy, R, Holloway, JW, Ghantous, A, Merid, SK, Bakulski, KM, Küpers, LK, Zhang, H, Richmond, RC, Page, CM, Duijts, L, Lie, RT, Melton, PE, Vonk, JM, Nohr, EA, Williams-DeVane, C, Huen, K, Rifas-Shiman, SL, Ruiz-Arenas, C, Gonseth, S, Rezwan, FI, Herceg, Z, Ekström, S, Croen, L, Falahi, F, Perron, P, Karagas, MR, Quraishi, BM, Suderman, M, Magnus, MC, Jaddoe, VWV, Taylor, JA, Anderson, D, Zhao, S, Smit, HA, Josey, MJ, Bradman, A, Baccarelli, AA, Bustamante, M, Håberg, SE, Pershagen, G, Hertz-Picciotto, I, Newschaffer, C, Corpeleijn, E, Bouchard, L, Lawlor, DA, Maguire, RL, Barcellos, LF, Davey Smith, G, Eskenazi, B, Karmaus, W, Marsit, CJ, Hivert, M-F, Snieder, H, Fallin, MD, Melén, E, Munthe-Kaas, MC, Arshad, H, Wiemels, JL, Annesi-Maesano, I, Vrijheid, M, Oken, E, Holland, N, Murphy, SK, Sørensen, TIA, Koppelman, GH, Newnham, JP, Wilcox, AJ, Nystad, W, London, SJ, Felix, JF & Relton, CL 2017, '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, vol 26, no. 20, pp. 4067-4085. DOI: 10.1093/hmg/ddx290

Standard

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 W V; 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 I A; Koppelman, Gerard H; Newnham, John P; Wilcox, Allen J; Nystad, Wenche; London, Stephanie J; Felix, Janine F; Relton, Caroline L.

In: Human Molecular Genetics, Vol. 26, No. 20, 15.10.2017, p. 4067-4085.

Research output: Contribution to journalArticle

Vancouver

Sharp GC, Salas LA, Monnereau C, Allard C, Yousefi P, Everson TM et al. 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. 2017 Oct 15;26(20):4067-4085. Available from, DOI: 10.1093/hmg/ddx290


BibTeX

@article{7d1356b094d449319684d4f1308595f7,
title = "Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium",
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.",
keywords = "BODY-MASS INDEX, GESTATIONAL WEIGHT-GAIN, CORD BLOOD, NORWEGIAN MOTHER, GENETIC-VARIANTS, CHILDREN ALSPAC, COHORT PROFILE, GENERATION R, BIRTH COHORT, EARLY-LIFE",
author = "Sharp, {Gemma C} and Salas, {Lucas A} and Claire Monnereau and Catherine Allard and Paul Yousefi and Everson, {Todd M} and Jon Bohlin and Zongli Xu and Rae-Chi Huang and Reese, {Sarah E} and Cheng-Jian Xu and Nour Ba{\"i}z and Cathrine Hoyo and Golareh Agha and Ritu Roy and Holloway, {John W} and Akram Ghantous and Merid, {Simon K} and Bakulski, {Kelly M} and K{\"u}pers, {Leanne K} and Hongmei Zhang and Richmond, {Rebecca C} and Page, {Christian M} and Liesbeth Duijts and Lie, {Rolv T} and Melton, {Phillip E} and Vonk, {Judith M} and Nohr, {Ellen A} and ClarLynda Williams-DeVane and Karen Huen and Rifas-Shiman, {Sheryl L} and Carlos Ruiz-Arenas and Semira Gonseth and Rezwan, {Faisal I} and Zdenko Herceg and Sandra Ekstr{\"o}m and Lisa Croen and Fahimeh Falahi and Patrice Perron and Karagas, {Margaret R} and Quraishi, {Bilal M} and Matthew Suderman and Magnus, {Maria C} and Jaddoe, {Vincent W V} and Taylor, {Jack A} and Denise Anderson and Shanshan Zhao and Smit, {Henriette A} and Josey, {Michele J} and Asa Bradman and Baccarelli, {Andrea A} and Mariona Bustamante and H{\aa}berg, {Siri E} and G{\"o}ran Pershagen and Irva Hertz-Picciotto and Craig Newschaffer and Eva Corpeleijn and Luigi Bouchard and Lawlor, {Debbie A} and Maguire, {Rachel L} and Barcellos, {Lisa F} and {Davey Smith}, George and Brenda Eskenazi and Wilfried Karmaus and Marsit, {Carmen J} and Marie-France Hivert and Harold Snieder and Fallin, {M Daniele} and Erik Mel{\'e}n and Munthe-Kaas, {Monica C} and Hasan Arshad and Wiemels, {Joseph L} and Isabella Annesi-Maesano and Martine Vrijheid and Emily Oken and Nina Holland and Murphy, {Susan K} and S{\o}rensen, {Thorkild I A} and Koppelman, {Gerard H} and Newnham, {John P} and Wilcox, {Allen J} and Wenche Nystad and London, {Stephanie J} and Felix, {Janine F} and Relton, {Caroline L}",
note = "{\circledC} The Author 2017. Published by Oxford University Press.",
year = "2017",
month = "10",
day = "15",
doi = "10.1093/hmg/ddx290",
language = "English",
volume = "26",
pages = "4067--4085",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "20",

}

RIS

TY - JOUR

T1 - Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation

T2 - Human Molecular Genetics

AU - Sharp,Gemma C

AU - Salas,Lucas A

AU - Monnereau,Claire

AU - Allard,Catherine

AU - Yousefi,Paul

AU - Everson,Todd M

AU - Bohlin,Jon

AU - Xu,Zongli

AU - Huang,Rae-Chi

AU - Reese,Sarah E

AU - Xu,Cheng-Jian

AU - Baïz,Nour

AU - Hoyo,Cathrine

AU - Agha,Golareh

AU - Roy,Ritu

AU - Holloway,John W

AU - Ghantous,Akram

AU - Merid,Simon K

AU - Bakulski,Kelly M

AU - Küpers,Leanne K

AU - Zhang,Hongmei

AU - Richmond,Rebecca C

AU - Page,Christian M

AU - Duijts,Liesbeth

AU - Lie,Rolv T

AU - Melton,Phillip E

AU - Vonk,Judith M

AU - Nohr,Ellen A

AU - Williams-DeVane,ClarLynda

AU - Huen,Karen

AU - Rifas-Shiman,Sheryl L

AU - Ruiz-Arenas,Carlos

AU - Gonseth,Semira

AU - Rezwan,Faisal I

AU - Herceg,Zdenko

AU - Ekström,Sandra

AU - Croen,Lisa

AU - Falahi,Fahimeh

AU - Perron,Patrice

AU - Karagas,Margaret R

AU - Quraishi,Bilal M

AU - Suderman,Matthew

AU - Magnus,Maria C

AU - Jaddoe,Vincent W V

AU - Taylor,Jack A

AU - Anderson,Denise

AU - Zhao,Shanshan

AU - Smit,Henriette A

AU - Josey,Michele J

AU - Bradman,Asa

AU - Baccarelli,Andrea A

AU - Bustamante,Mariona

AU - Håberg,Siri E

AU - Pershagen,Göran

AU - Hertz-Picciotto,Irva

AU - Newschaffer,Craig

AU - Corpeleijn,Eva

AU - Bouchard,Luigi

AU - Lawlor,Debbie A

AU - Maguire,Rachel L

AU - Barcellos,Lisa F

AU - Davey Smith,George

AU - Eskenazi,Brenda

AU - Karmaus,Wilfried

AU - Marsit,Carmen J

AU - Hivert,Marie-France

AU - Snieder,Harold

AU - Fallin,M Daniele

AU - Melén,Erik

AU - Munthe-Kaas,Monica C

AU - Arshad,Hasan

AU - Wiemels,Joseph L

AU - Annesi-Maesano,Isabella

AU - Vrijheid,Martine

AU - Oken,Emily

AU - Holland,Nina

AU - Murphy,Susan K

AU - Sørensen,Thorkild I A

AU - Koppelman,Gerard H

AU - Newnham,John P

AU - Wilcox,Allen J

AU - Nystad,Wenche

AU - London,Stephanie J

AU - Felix,Janine F

AU - Relton,Caroline L

N1 - © The Author 2017. Published by Oxford University Press.

PY - 2017/10/15

Y1 - 2017/10/15

N2 - 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.

AB - 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.

KW - BODY-MASS INDEX

KW - GESTATIONAL WEIGHT-GAIN

KW - CORD BLOOD

KW - NORWEGIAN MOTHER

KW - GENETIC-VARIANTS

KW - CHILDREN ALSPAC

KW - COHORT PROFILE

KW - GENERATION R

KW - BIRTH COHORT

KW - EARLY-LIFE

U2 - 10.1093/hmg/ddx290

DO - 10.1093/hmg/ddx290

M3 - Article

VL - 26

SP - 4067

EP - 4085

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 20

ER -

ID: 49047748