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1. Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation

Author

Sammallahti, S. (Sara), Cortes Hidalgo, A. P. (Andrea P.), Tuominen, S. (Samuli), Malmberg, A. (Anni), Mulder, R. H. (Rosa H.), Brunst, K. J. (Kelly J.), Alemany, S. (Silvia), McBride, N. S. (Nancy S.), Yousefi, P. (Paul), Heiss, J. A. (Jonathan A.), McRae, N. (Nia), Page, C. M. (Christian M.), Jin, J. (Jianping), Pesce, G. (Giancarlo), Caramaschi, D. (Doretta), Rifas-Shiman, S. L. (Sheryl L.), Koen, N. (Nastassja), Adams, C. D. (Charleen D.), Magnus, M. C. (Maria C.), Baiz, N. (Nour), Ratanatharathorn, A. (Andrew), Czamara, D. (Darina), Haberg, S. E. (Siri E.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Cardenas, A. (Andres), DeMeo, D. L. (Dawn L.), Lawlor, D. A. (Deborah A.), Relton, C. L. (Caroline L.), Felix, J. F. (Janine F.), van IJzendoorn, M. H. (Marinus H.), Bakermans-Kranenburg, M. J. (Marian J.), Kajantie, E. (Eero), Raikkonen, K. (Katri), Sunyer, J. (Jordi), Sharp, G. C. (Gemma C.), Houtepen, L. C. (Lotte C.), Nohr, E. A. (Ellen A.), Sorensen, T. I. (Thorkild I. A.), Tellez-Rojo, M. M. (Martha M.), Wright, R. O. (Robert O.), Annesi-Maesano, I. (Isabella), Wright, J. (John), Hivert, M.-F. (Marie-France), Wright, R. J. (Rosalind J.), Zar, H. J. (Heather J.), Stein, D. J. (Dan J.), London, S. J. (Stephanie J.), Cecil, C. A. (Charlotte A. M.), Tiemeier, H. (Henning), Lahti, J. (Jari), Sammallahti, S. (Sara), Cortes Hidalgo, A. P. (Andrea P.), Tuominen, S. (Samuli), Malmberg, A. (Anni), Mulder, R. H. (Rosa H.), Brunst, K. J. (Kelly J.), Alemany, S. (Silvia), McBride, N. S. (Nancy S.), Yousefi, P. (Paul), Heiss, J. A. (Jonathan A.), McRae, N. (Nia), Page, C. M. (Christian M.), Jin, J. (Jianping), Pesce, G. (Giancarlo), Caramaschi, D. (Doretta), Rifas-Shiman, S. L. (Sheryl L.), Koen, N. (Nastassja), Adams, C. D. (Charleen D.), Magnus, M. C. (Maria C.), Baiz, N. (Nour), Ratanatharathorn, A. (Andrew), Czamara, D. (Darina), Haberg, S. E. (Siri E.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Cardenas, A. (Andres), DeMeo, D. L. (Dawn L.), Lawlor, D. A. (Deborah A.), Relton, C. L. (Caroline L.), Felix, J. F. (Janine F.), van IJzendoorn, M. H. (Marinus H.), Bakermans-Kranenburg, M. J. (Marian J.), Kajantie, E. (Eero), Raikkonen, K. (Katri), Sunyer, J. (Jordi), Sharp, G. C. (Gemma C.), Houtepen, L. C. (Lotte C.), Nohr, E. A. (Ellen A.), Sorensen, T. I. (Thorkild I. A.), Tellez-Rojo, M. M. (Martha M.), Wright, R. O. (Robert O.), Annesi-Maesano, I. (Isabella), Wright, J. (John), Hivert, M.-F. (Marie-France), Wright, R. J. (Rosalind J.), Zar, H. J. (Heather J.), Stein, D. J. (Dan J.), London, S. J. (Stephanie J.), Cecil, C. A. (Charlotte A. M.), Tiemeier, H. (Henning), and Lahti, J. (Jari)

Abstract

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

Published
2021

2. DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies

Author

Vehmeijer, F.O.L. (Florianne O.L.), Küpers, A.M. (Marlijn), Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Lent, S. (Samantha), Jima, D.D. (Dereje D.), Tindula, G. (Gwen), Reese, S.E. (Sarah E.), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F.I. (Faisal I.), Melton, P.E. (Philip E.), Nohr, C. (Christian), Escaramís, G. (Geòrgia), Rzehak, P. (Peter), Heiskala, A. (Anni), Gong, T. (Tong), Tuominen, S.T. (Samuli T.), Gao, L. (Lu), Ross, J.P. (Jason P.), Starling, A.P. (Anne P.), Holloway, J.W. (John W.), Yousefi, P. (Paul), Aasvang, G.M. (Gunn Marit), Beilin, L.J. (Lawrence), Bergström, A. (Anna), Binder, E.B. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (B.), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Håberg, S.E. (Siri E), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, C.A. (Christian), Langhendries, J.P. (Jean Paul), Lepeule, J. (Johanna), Magnus, M.C. (Maria C.), Maguire, R.L. (Rachel L.), Molloy, P.L. (Peter L.), Poppelaars-Monnereau, C. (Claire), Mori, T.A. (Trevor A.), Oken, E. (Emily), Räikkönen, K. (Katri), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J.M. (Judith), Xu, C.-J. (Cheng-Jian), Yang, I.V. (Ivana V.), Zhang, H. (Hongmei), Zhang, W. (Weiming), Karmaus, W. (Wilfried), Dabelea, D. (Dana), Muhlhausler, B.S. (Beverly S.), Breton, C. (Carrie), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sørensen, T.I.A. (Thorkild), Huang, R.-C. (Rae-Chi), Arshad, S.H. (Syed), Nystad, W. (Wenche), Melén, E. (Erik), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S.K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A.A. (Andrea), Relton, C.L. (Caroline), Snieder, H. (Harold), Jaddoe, V.W.V. (Vincent), Felix, J.F. (Janine), Vehmeijer, F.O.L. (Florianne O.L.), Küpers, A.M. (Marlijn), Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Lent, S. (Samantha), Jima, D.D. (Dereje D.), Tindula, G. (Gwen), Reese, S.E. (Sarah E.), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F.I. (Faisal I.), Melton, P.E. (Philip E.), Nohr, C. (Christian), Escaramís, G. (Geòrgia), Rzehak, P. (Peter), Heiskala, A. (Anni), Gong, T. (Tong), Tuominen, S.T. (Samuli T.), Gao, L. (Lu), Ross, J.P. (Jason P.), Starling, A.P. (Anne P.), Holloway, J.W. (John W.), Yousefi, P. (Paul), Aasvang, G.M. (Gunn Marit), Beilin, L.J. (Lawrence), Bergström, A. (Anna), Binder, E.B. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (B.), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Håberg, S.E. (Siri E), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, C.A. (Christian), Langhendries, J.P. (Jean Paul), Lepeule, J. (Johanna), Magnus, M.C. (Maria C.), Maguire, R.L. (Rachel L.), Molloy, P.L. (Peter L.), Poppelaars-Monnereau, C. (Claire), Mori, T.A. (Trevor A.), Oken, E. (Emily), Räikkönen, K. (Katri), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J.M. (Judith), Xu, C.-J. (Cheng-Jian), Yang, I.V. (Ivana V.), Zhang, H. (Hongmei), Zhang, W. (Weiming), Karmaus, W. (Wilfried), Dabelea, D. (Dana), Muhlhausler, B.S. (Beverly S.), Breton, C. (Carrie), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sørensen, T.I.A. (Thorkild), Huang, R.-C. (Rae-Chi), Arshad, S.H. (Syed), Nystad, W. (Wenche), Melén, E. (Erik), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S.K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A.A. (Andrea), Relton, C.L. (Caroline), Snieder, H. (Harold), Jaddoe, V.W.V. (Vincent), and Felix, J.F. (Janine)

Abstract

Background: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10−7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10−4; adolescence Penrichment = 2.10 × 10−7). Conclusions: There were only minimal associations of DNA methylation with childhood and adolescent BMI.

Published
2020
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3. DNA methylation and body mass index from birth to adolescence:meta-analyses of epigenome-wide association studies

Author

Vehmeijer, F. O. (Florianne O. L.), Kuepers, L. K. (Leanne K.), Sharp, G. C. (Gemma C.), Salas, L. A. (Lucas A.), Lent, S. (Samantha), Jima, D. D. (Dereje D.), Tindula, G. (Gwen), Reese, S. (Sarah), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F. I. (Faisal, I), Melton, P. E. (Philip E.), Nohr, E. (Ellen), Escaramis, G. (Georgia), Rzehak, P. (Peter), Heiskala, A. (Anni), Gong, T. (Tong), Tuominen, S. T. (Samuli T.), Gao, L. (Lu), Ross, J. P. (Jason P.), Starling, A. P. (Anne P.), Holloway, J. W. (John W.), Yousefi, P. (Paul), Aasvang, G. M. (Gunn Marit), Beilin, L. J. (Lawrence J.), Bergstrom, A. (Anna), Binder, E. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (Brenda), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Haberg, S. E. (Siri E.), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, I. (Inger), Langhendries, J.-P. (Jean-Paul), Lepeule, J. (Johanna), Magnus, M. C. (Maria C.), Maguire, R. L. (Rachel L.), Molloy, P. L. (Peter L.), Monnereau, C. (Claire), Mori, T. A. (Trevor A.), Oken, E. (Emily), Raikkonen, K. (Katri), Rifas-Shiman, S. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J. M. (Judith M.), Xu, C.-j. (Cheng-jian), Yang, I. V. (Ivana, V), Zhang, H. (Hongmei), Zhang, W. (Weiming), Karmaus, W. (Wilfried), Dabelea, D. (Dana), Muhlhausler, B. S. (Beverly S.), Breton, C. V. (Carrie, V), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sorensen, T. I. (Thorkild I. A.), Huang, R.-C. (Rae-Chi), Arshad, S. H. (Syed Hasan), Nystad, W. (Wenche), Melen, E. (Erik), Koppelman, G. H. (Gerard H.), London, S. J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S. K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A. (Andrea), Relton, C. L. (Caroline L.), Snieder, H. (Harold), Jaddoe, V. W. (Vincent W. V.), Felix, J. F. (Janine F.), Vehmeijer, F. O. (Florianne O. L.), Kuepers, L. K. (Leanne K.), Sharp, G. C. (Gemma C.), Salas, L. A. (Lucas A.), Lent, S. (Samantha), Jima, D. D. (Dereje D.), Tindula, G. (Gwen), Reese, S. (Sarah), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F. I. (Faisal, I), Melton, P. E. (Philip E.), Nohr, E. (Ellen), Escaramis, G. (Georgia), Rzehak, P. (Peter), Heiskala, A. (Anni), Gong, T. (Tong), Tuominen, S. T. (Samuli T.), Gao, L. (Lu), Ross, J. P. (Jason P.), Starling, A. P. (Anne P.), Holloway, J. W. (John W.), Yousefi, P. (Paul), Aasvang, G. M. (Gunn Marit), Beilin, L. J. (Lawrence J.), Bergstrom, A. (Anna), Binder, E. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (Brenda), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Haberg, S. E. (Siri E.), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, I. (Inger), Langhendries, J.-P. (Jean-Paul), Lepeule, J. (Johanna), Magnus, M. C. (Maria C.), Maguire, R. L. (Rachel L.), Molloy, P. L. (Peter L.), Monnereau, C. (Claire), Mori, T. A. (Trevor A.), Oken, E. (Emily), Raikkonen, K. (Katri), Rifas-Shiman, S. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J. M. (Judith M.), Xu, C.-j. (Cheng-jian), Yang, I. V. (Ivana, V), Zhang, H. (Hongmei), Zhang, W. (Weiming), Karmaus, W. (Wilfried), Dabelea, D. (Dana), Muhlhausler, B. S. (Beverly S.), Breton, C. V. (Carrie, V), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sorensen, T. I. (Thorkild I. A.), Huang, R.-C. (Rae-Chi), Arshad, S. H. (Syed Hasan), Nystad, W. (Wenche), Melen, E. (Erik), Koppelman, G. H. (Gerard H.), London, S. J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S. K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A. (Andrea), Relton, C. L. (Caroline L.), Snieder, H. (Harold), Jaddoe, V. W. (Vincent W. V.), and Felix, J. F. (Janine F.)

Abstract

Background: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10⁻⁷, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10⁻⁴; adolescence Penrichment = 2.10 × 10⁻⁷). Conclusions: There were only minimal associations of DNA methylation with childhood and adol

Published
2020

4. Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis

Author

Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Yousefi, P. (Paul), Relton, C.L. (Caroline), Merid, S.K. (Simon Kebede), Breton, C. (Carrie), Gao, L. (Lu), Volk, H.E. (Heather E.), Feinberg, J.I. (Jason I.), Ladd-Acosta, C. (Christine), Bakulski, K. (Kelly), Auffray, C. (C.), Lemonnier, N. (Nathanaël), Plusquin, M. (Michelle), Ghantous, A. (Akram), Herceg, Z. (Zdenko), Nawrot, T.S. (Tim S.), Pizzi, C. (Costanza), Richiardi, L. (Lorenzo), Rusconi, F. (Franca), Vineis, P. (Paolo), Kogevinas, M. (Manolis), Felix, J.F. (Janine), Duijts, L. (Liesbeth), Dekker, H.T. (Herman) den, Jaddoe, V.W.V. (Vincent), Ruiz, J.L. (José L), Bustamante, M. (Mariona), Anto, J.M. (Josep), Sunyer, J. (Jordi), Vrijheid, M. (Martine), Gutzkow, K.B. (Kristine B.), Grazuleviciene, R. (Regina), Hernandez-Ferrer, C. (Carles), Annesi-Maesano, I. (Isabella), Lepeule, J. (Johanna), Bousquet, J. (Jean), Bergström, A. (Anna), Kull, C.A. (Christian), Söderhäll, C. (Cilla), Kere, J. (Juha), Gehring, U. (Ulrike), Brunekreef, B. (Bert), Just, A.C. (Allan C.), Wright, R.J. (Rosalind J.), Peng, C. (Cheng), Gold, D.R. (Diane), Kloog, I. (Itai), Demeo, D.L. (Dawn), Pershagen, G. (Göran), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Baccarelli, A.A. (Andrea), Melén, E. (Erik), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Yousefi, P. (Paul), Relton, C.L. (Caroline), Merid, S.K. (Simon Kebede), Breton, C. (Carrie), Gao, L. (Lu), Volk, H.E. (Heather E.), Feinberg, J.I. (Jason I.), Ladd-Acosta, C. (Christine), Bakulski, K. (Kelly), Auffray, C. (C.), Lemonnier, N. (Nathanaël), Plusquin, M. (Michelle), Ghantous, A. (Akram), Herceg, Z. (Zdenko), Nawrot, T.S. (Tim S.), Pizzi, C. (Costanza), Richiardi, L. (Lorenzo), Rusconi, F. (Franca), Vineis, P. (Paolo), Kogevinas, M. (Manolis), Felix, J.F. (Janine), Duijts, L. (Liesbeth), Dekker, H.T. (Herman) den, Jaddoe, V.W.V. (Vincent), Ruiz, J.L. (José L), Bustamante, M. (Mariona), Anto, J.M. (Josep), Sunyer, J. (Jordi), Vrijheid, M. (Martine), Gutzkow, K.B. (Kristine B.), Grazuleviciene, R. (Regina), Hernandez-Ferrer, C. (Carles), Annesi-Maesano, I. (Isabella), Lepeule, J. (Johanna), Bousquet, J. (Jean), Bergström, A. (Anna), Kull, C.A. (Christian), Söderhäll, C. (Cilla), Kere, J. (Juha), Gehring, U. (Ulrike), Brunekreef, B. (Bert), Just, A.C. (Allan C.), Wright, R.J. (Rosalind J.), Peng, C. (Cheng), Gold, D.R. (Diane), Kloog, I. (Itai), Demeo, D.L. (Dawn), Pershagen, G. (Göran), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Baccarelli, A.A. (Andrea), and Melén, E. (Erik)

Abstract

BACKGROUND: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. OBJECTIVES: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children. METHODS: We meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. RESULTS: Six CpGs were significantly associa

Published
2019
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5. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Author

Kupers, L. K. (Leanne K.), Monnereau, C. (Claire), Sharp, G. C. (Gemma C.), Yousefi, P. (Paul), Salas, L. A. (Lucas A.), Ghantous, A. (Akram), Page, C. M. (Christian M.), Reese, S. E. (Sarah E.), Wilcox, A. J. (Allen J.), Czamara, D. (Darina), Starling, A. P. (Anne P.), Novoloaca, A. (Alexei), Lent, S. (Samantha), Roy, R. (Ritu), Hoyo, C. (Cathrine), Breton, C. V. (Carrie, V), Allard, C. (Catherine), Just, A. C. (Allan C.), Bakulski, K. M. (Kelly M.), Holloway, J. W. (John W.), Everson, T. M. (Todd M.), Xu, C.-J. (Cheng-Jian), Huang, R.-C. (Rae-Chi), van der Plaat, D. A. (Diana A.), Wielscher, M. (Matthias), Merid, S. K. (Simon Kebede), Ullemar, V. (Vilhelmina), Rezwan, F. I. (Faisal, I), Lahti, J. (Jari), van Dongen, J. (Jenny), Langie, S. A. (Sabine A. S.), Richardson, T. G. (Tom G.), Magnus, M. C. (Maria C.), Nohr, E. A. (Ellen A.), Xu, Z. (Zongli), Duijts, L. (Liesbeth), Zhao, S. (Shanshan), Zhang, W. (Weiming), Plusquin, M. (Michelle), DeMeo, D. L. (Dawn L.), Solomon, O. (Olivia), Heimovaara, J. H. (Joosje H.), Jima, D. D. (Dereje D.), Gao, L. (Lu), Bustamante, M. (Mariona), Perron, P. (Patrice), Wright, R. O. (Robert O.), Hertz-Picciotto, I. (Irva), Zhang, H. (Hongmei), Karagas, M. R. (Margaret R.), Gehring, U. (Ulrike), Marsit, C. J. (Carmen J.), Beilin, L. J. (Lawrence J.), Vonk, J. M. (Judith M.), Jarvelin, M.-R. (Marjo-Riitta), Bergstrom, A. (Anna), Ortqvist, A. K. (Anne K.), Ewart, S. (Susan), Villa, P. M. (Pia M.), Moore, S. E. (Sophie E.), Willemsen, G. (Gonneke), Standaert, A. R. (Arnout R. L.), Haberg, S. E. (Siri E.), Sorensen, T. I. (Thorkild I. A.), Taylor, J. A. (Jack A.), Raikkonen, K. (Katri), Yang, I. V. (Ivana, V), Kechris, K. (Katerina), Nawrot, T. S. (Tim S.), Silver, M. J. (Matt J.), Gong, Y. Y. (Yun Yun), Richiardi, L. (Lorenzo), Kogevinas, M. (Manolis), Litonjua, A. A. (Augusto A.), Eskenazi, B. (Brenda), Huen, K. (Karen), Mbarek, H. (Hamdi), Maguire, R. L. (Rachel L.), Dwyer, T. (Terence), Vrijheid, M. (Martine), Bouchard, L. (Luigi), Baccarelli, A. A. (Andrea A.), Croen, L. A. (Lisa A.), Karmaus, W. (Wilfried), Anderson, D. (Denise), de Vries, M. (Maaike), Sebert, S. (Sylvain), Kere, J. (Juha), Karlsson, R. (Robert), Arshad, S. H. (Syed Hasan), Hamalainen, E. (Esa), Routledge, M. N. (Michael N.), Boomsma, D. I. (Dorret, I), Feinberg, A. P. (Andrew P.), Newschaffer, C. J. (Craig J.), Govarts, E. (Eva), Moisse, M. (Matthieu), Fallin, M. D. (M. Daniele), Melen, E. (Erik), Prentice, A. M. (Andrew M.), Kajantie, E. (Eero), Almqvist, C. (Catarina), Oken, E. (Emily), Dabelea, D. (Dana), Boezen, H. M. (H. Marike), Melton, P. E. (Phillip E.), Wright, R. J. (Rosalind J.), Koppelman, G. H. (Gerard H.), Trevisi, L. (Letizia), Hivert, M.-F. (Marie-France), Sunyer, J. (Jordi), Munthe-Kaas, M. C. (Monica C.), Murphy, S. K. (Susan K.), Corpeleijn, E. (Eva), Wiemels, J. (Joseph), Holland, N. (Nina), Herceg, Z. (Zdenko), Binder, E. B. (Elisabeth B.), Smith, G. D. (George Davey), Jaddoe, V. W. (Vincent W. V.), Lie, R. T. (Rolv T.), Nystad, W. (Wenche), London, S. J. (Stephanie J.), Lawlor, D. A. (Debbie A.), Relton, C. L. (Caroline L.), Snieder, H. (Harold), Felix, J. F. (Janine F.), Kupers, L. K. (Leanne K.), Monnereau, C. (Claire), Sharp, G. C. (Gemma C.), Yousefi, P. (Paul), Salas, L. A. (Lucas A.), Ghantous, A. (Akram), Page, C. M. (Christian M.), Reese, S. E. (Sarah E.), Wilcox, A. J. (Allen J.), Czamara, D. (Darina), Starling, A. P. (Anne P.), Novoloaca, A. (Alexei), Lent, S. (Samantha), Roy, R. (Ritu), Hoyo, C. (Cathrine), Breton, C. V. (Carrie, V), Allard, C. (Catherine), Just, A. C. (Allan C.), Bakulski, K. M. (Kelly M.), Holloway, J. W. (John W.), Everson, T. M. (Todd M.), Xu, C.-J. (Cheng-Jian), Huang, R.-C. (Rae-Chi), van der Plaat, D. A. (Diana A.), Wielscher, M. (Matthias), Merid, S. K. (Simon Kebede), Ullemar, V. (Vilhelmina), Rezwan, F. I. (Faisal, I), Lahti, J. (Jari), van Dongen, J. (Jenny), Langie, S. A. (Sabine A. S.), Richardson, T. G. (Tom G.), Magnus, M. C. (Maria C.), Nohr, E. A. (Ellen A.), Xu, Z. (Zongli), Duijts, L. (Liesbeth), Zhao, S. (Shanshan), Zhang, W. (Weiming), Plusquin, M. (Michelle), DeMeo, D. L. (Dawn L.), Solomon, O. (Olivia), Heimovaara, J. H. (Joosje H.), Jima, D. D. (Dereje D.), Gao, L. (Lu), Bustamante, M. (Mariona), Perron, P. (Patrice), Wright, R. O. (Robert O.), Hertz-Picciotto, I. (Irva), Zhang, H. (Hongmei), Karagas, M. R. (Margaret R.), Gehring, U. (Ulrike), Marsit, C. J. (Carmen J.), Beilin, L. J. (Lawrence J.), Vonk, J. M. (Judith M.), Jarvelin, M.-R. (Marjo-Riitta), Bergstrom, A. (Anna), Ortqvist, A. K. (Anne K.), Ewart, S. (Susan), Villa, P. M. (Pia M.), Moore, S. E. (Sophie E.), Willemsen, G. (Gonneke), Standaert, A. R. (Arnout R. L.), Haberg, S. E. (Siri E.), Sorensen, T. I. (Thorkild I. A.), Taylor, J. A. (Jack A.), Raikkonen, K. (Katri), Yang, I. V. (Ivana, V), Kechris, K. (Katerina), Nawrot, T. S. (Tim S.), Silver, M. J. (Matt J.), Gong, Y. Y. (Yun Yun), Richiardi, L. (Lorenzo), Kogevinas, M. (Manolis), Litonjua, A. A. (Augusto A.), Eskenazi, B. (Brenda), Huen, K. (Karen), Mbarek, H. (Hamdi), Maguire, R. L. (Rachel L.), Dwyer, T. (Terence), Vrijheid, M. (Martine), Bouchard, L. (Luigi), Baccarelli, A. A. (Andrea A.), Croen, L. A. (Lisa A.), Karmaus, W. (Wilfried), Anderson, D. (Denise), de Vries, M. (Maaike), Sebert, S. (Sylvain), Kere, J. (Juha), Karlsson, R. (Robert), Arshad, S. H. (Syed Hasan), Hamalainen, E. (Esa), Routledge, M. N. (Michael N.), Boomsma, D. I. (Dorret, I), Feinberg, A. P. (Andrew P.), Newschaffer, C. J. (Craig J.), Govarts, E. (Eva), Moisse, M. (Matthieu), Fallin, M. D. (M. Daniele), Melen, E. (Erik), Prentice, A. M. (Andrew M.), Kajantie, E. (Eero), Almqvist, C. (Catarina), Oken, E. (Emily), Dabelea, D. (Dana), Boezen, H. M. (H. Marike), Melton, P. E. (Phillip E.), Wright, R. J. (Rosalind J.), Koppelman, G. H. (Gerard H.), Trevisi, L. (Letizia), Hivert, M.-F. (Marie-France), Sunyer, J. (Jordi), Munthe-Kaas, M. C. (Monica C.), Murphy, S. K. (Susan K.), Corpeleijn, E. (Eva), Wiemels, J. (Joseph), Holland, N. (Nina), Herceg, Z. (Zdenko), Binder, E. B. (Elisabeth B.), Smith, G. D. (George Davey), Jaddoe, V. W. (Vincent W. V.), Lie, R. T. (Rolv T.), Nystad, W. (Wenche), London, S. J. (Stephanie J.), Lawlor, D. A. (Debbie A.), Relton, C. L. (Caroline L.), Snieder, H. (Harold), and Felix, J. F. (Janine F.)

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 < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Published
2019

6. Cohort profile: Pregnancy and childhood epigenetics (PACE) consortium

Author

Felix, J.F. (Janine F.), Joubert, B.R. (Bonnie), Baccarelli, A.A. (Andrea), Sharp, G.C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baïz, N. (Nour), Bakermans-Kranenburg, M.J. (Marian), Bakulski, K.M. (Kelly M.), Binder, E.B. (Elisabeth), Bouchard, L. (Luigi), Breton, C. (Carrie), Brunekreef, B. (Bert), Brunst, K.J. (Kelly J.), Burchard, E.G. (Esteban), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M.C. (Monica Cheng), Corpeleijn, W.E. (Willemijn), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G.D. (George Davey), Boever, P. (Patrick) de, Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (B.), Everson, T.M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M.D. (M. Daniele), Farchi, S. (Sara), Fernandez, M.F. (Mariana), Gao, L. (Lu), Gaunt, T.R. (Tom), Ghantous, A. (Akram), Gillman, M.W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Håberg, S.E. (Siri E), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J.W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D.D. (Dereje D.), Just, A.C. (Allan C.), Karagas, M.R. (Margaret), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K.J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G.H. (Gerard), Küpers, A.M. (Marlijn), Ladd-Acosta, C. (Christine), Lahti, J., Lambrechts, N. (Nathalie), Langie, S.A.S. (Sabine A.S.), Lie, R.T. (Rolv T.), Liu, A.H. (Andrew H.), Magnus, M.C. (Maria C.), Magnus, P. (Per), Maguire, R.L. (Rachel L.), Marsit, C.J. (Carmen J.), McArdle, W.L. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S.K. (Susan K.), Nawrot, T.S. (Tim S.), Nisticò, L. (Lorenza), Nohr, C. (Christian), Nordlund, B. (Björn), Nystad, W. (Wenche), Oh, S.S. (Sam S.), Oken, E. (Emily), Page, C.M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Göran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Räikkönen, K. (Katri), Reese, S.E. (Sarah E.), Reischl, G. (Gunilla), Richiardi, L. (Lorenzo), Ring, S.M. (Susan), Roy, R.P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D.A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Starling, A.P. (Anne P.), Sunyer, J. (Jordi), Taylor, J.A. (Jack A), Tiemeier, H.W. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), IJzendoorn, M.H. (Rien) van, Vonk, J.M. (Judith), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. (Joseph), Wilcox, A.J. (Allen), Wright, R.J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I.V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), London, S.J. (Stephanie J.), Felix, J.F. (Janine F.), Joubert, B.R. (Bonnie), Baccarelli, A.A. (Andrea), Sharp, G.C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baïz, N. (Nour), Bakermans-Kranenburg, M.J. (Marian), Bakulski, K.M. (Kelly M.), Binder, E.B. (Elisabeth), Bouchard, L. (Luigi), Breton, C. (Carrie), Brunekreef, B. (Bert), Brunst, K.J. (Kelly J.), Burchard, E.G. (Esteban), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M.C. (Monica Cheng), Corpeleijn, W.E. (Willemijn), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G.D. (George Davey), Boever, P. (Patrick) de, Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (B.), Everson, T.M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M.D. (M. Daniele), Farchi, S. (Sara), Fernandez, M.F. (Mariana), Gao, L. (Lu), Gaunt, T.R. (Tom), Ghantous, A. (Akram), Gillman, M.W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Håberg, S.E. (Siri E), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J.W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D.D. (Dereje D.), Just, A.C. (Allan C.), Karagas, M.R. (Margaret), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K.J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G.H. (Gerard), Küpers, A.M. (Marlijn), Ladd-Acosta, C. (Christine), Lahti, J., Lambrechts, N. (Nathalie), Langie, S.A.S. (Sabine A.S.), Lie, R.T. (Rolv T.), Liu, A.H. (Andrew H.), Magnus, M.C. (Maria C.), Magnus, P. (Per), Maguire, R.L. (Rachel L.), Marsit, C.J. (Carmen J.), McArdle, W.L. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S.K. (Susan K.), Nawrot, T.S. (Tim S.), Nisticò, L. (Lorenza), Nohr, C. (Christian), Nordlund, B. (Björn), Nystad, W. (Wenche), Oh, S.S. (Sam S.), Oken, E. (Emily), Page, C.M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Göran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Räikkönen, K. (Katri), Reese, S.E. (Sarah E.), Reischl, G. (Gunilla), Richiardi, L. (Lorenzo), Ring, S.M. (Susan), Roy, R.P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D.A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Starling, A.P. (Anne P.), Sunyer, J. (Jordi), Taylor, J.A. (Jack A), Tiemeier, H.W. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), IJzendoorn, M.H. (Rien) van, Vonk, J.M. (Judith), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. (Joseph), Wilcox, A.J. (Allen), Wright, R.J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I.V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), and London, S.J. (Stephanie J.)

Published
2018
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7. Cohort profile:pregnancy and childhood epigenetics (PACE) consortium

Author

Felix, J. F. (Janine F.), Joubert, B. R. (Bonnie R.), Baccarelli, A. A. (Andrea A.), Sharp, G. C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baiz, N. (Nour), Bakermans-Kranenburg, M. J. (Marian J.), Bakulski, K. M. (Kelly M.), Binder, E. B. (Elisabeth B.), Bouchard, L. (Luigi), Breton, C. V. (Carrie V.), Brunekreef, B. (Bert), Brunst, K. J. (Kelly J.), Burchard, E. G. (Esteban G.), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M. C. (Monica Cheng), Corpeleijn, E. (Eva), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G. D. (George Davey), De Boever, P. (Patrick), Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (Brenda), Everson, T. M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M. D. (M. Daniele), Farchi, S. (Sara), Fernandez, M. F. (Mariana F.), Gao, L. (Lu), Gaunt, T. R. (Tom R.), Ghantous, A. (Akram), Gillman, M. W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Haberg, S. E. (Siri E.), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J. W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D. D. (Dereje D.), Just, A. C. (Allan C.), Karagas, M. R. (Margaret R.), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K. J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G. H. (Gerard H.), Kupers, L. K. (Leanne K.), Ladd-Acosta, C. (Christine), Lahti, J. (Jari), Lambrechts, N. (Nathalie), Langie, S. A. (Sabine A. S.), Lie, R. T. (Rolv T.), Liu, A. H. (Andrew H.), Magnus, M. C. (Maria C.), Magnus, P. (Per), Maguire, R. L. (Rachel L.), Marsit, C. J. (Carmen J.), McArdle, W. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S. K. (Susan K.), Nawrot, T. S. (Tim S.), Nistico, L. (Lorenza), Nohr, E. A. (Ellen A.), Nordlund, B. (Bjorn), Nystad, W. (Wenche), Oh, S. S. (Sam S.), Oken, E. (Emily), Page, C. M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Goran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Raikkonen, K. (Katri), Reese, S. E. (Sarah E.), Reischl, E. (Eva), Richiardi, L. (Lorenzo), Ring, S. (Susan), Roy, R. P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D. A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sorensen, T. I. (Thorkild I. A.), Starling, A. P. (Anne P.), Sunyer, J. (Jordi), ATaylor, J. (Jack), Tiemeier, H. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), Van Ijzendoorn, M. H. (Marinus H.), Vonk, J. M. (Judith M.), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. L. (Joseph L.), Wilcox, A. J. (Allen J.), Wright, R. J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I. V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C. L. (Caroline L.), Jaddoe, V. W. (Vincent W. V.), London, S. J. (Stephanie J.), Felix, J. F. (Janine F.), Joubert, B. R. (Bonnie R.), Baccarelli, A. A. (Andrea A.), Sharp, G. C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baiz, N. (Nour), Bakermans-Kranenburg, M. J. (Marian J.), Bakulski, K. M. (Kelly M.), Binder, E. B. (Elisabeth B.), Bouchard, L. (Luigi), Breton, C. V. (Carrie V.), Brunekreef, B. (Bert), Brunst, K. J. (Kelly J.), Burchard, E. G. (Esteban G.), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M. C. (Monica Cheng), Corpeleijn, E. (Eva), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G. D. (George Davey), De Boever, P. (Patrick), Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (Brenda), Everson, T. M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M. D. (M. Daniele), Farchi, S. (Sara), Fernandez, M. F. (Mariana F.), Gao, L. (Lu), Gaunt, T. R. (Tom R.), Ghantous, A. (Akram), Gillman, M. W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Haberg, S. E. (Siri E.), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J. W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D. D. (Dereje D.), Just, A. C. (Allan C.), Karagas, M. R. (Margaret R.), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K. J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G. H. (Gerard H.), Kupers, L. K. (Leanne K.), Ladd-Acosta, C. (Christine), Lahti, J. (Jari), Lambrechts, N. (Nathalie), Langie, S. A. (Sabine A. S.), Lie, R. T. (Rolv T.), Liu, A. H. (Andrew H.), Magnus, M. C. (Maria C.), Magnus, P. (Per), Maguire, R. L. (Rachel L.), Marsit, C. J. (Carmen J.), McArdle, W. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S. K. (Susan K.), Nawrot, T. S. (Tim S.), Nistico, L. (Lorenza), Nohr, E. A. (Ellen A.), Nordlund, B. (Bjorn), Nystad, W. (Wenche), Oh, S. S. (Sam S.), Oken, E. (Emily), Page, C. M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Goran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Raikkonen, K. (Katri), Reese, S. E. (Sarah E.), Reischl, E. (Eva), Richiardi, L. (Lorenzo), Ring, S. (Susan), Roy, R. P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D. A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sorensen, T. I. (Thorkild I. A.), Starling, A. P. (Anne P.), Sunyer, J. (Jordi), ATaylor, J. (Jack), Tiemeier, H. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), Van Ijzendoorn, M. H. (Marinus H.), Vonk, J. M. (Judith M.), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. L. (Joseph L.), Wilcox, A. J. (Allen J.), Wright, R. J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I. V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C. L. (Caroline L.), Jaddoe, V. W. (Vincent W. V.), and London, S. J. (Stephanie J.)

Published
2018

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

Author

Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Poppelaars-Monnereau, C. (Claire), Allard, C. (Catherine), Yousefi, P. (Paul), Everson, T.M. (Todd M.), Bohlin, J. (Jon), Xu, Z. (Zongli), Huang, R.-C. (Rae-Chi), Reese, S.E. (Sarah E.), Xu, C.-J. (Cheng-Jian), Baïz, N. (Nour), Hoyo, C. (Cathrine), Agha, G. (Golareh), Roy, R. (Ritu), Holloway, J. (John), Ghantous, A. (Akram), Merid, S.K. (Simon Kebede), Bakulski, K.M. (Kelly M.), Küpers, A.M. (Marlijn), Zhang, H. (Hongmei), Richmond, R.C. (Rebecca C.), Page, C.M. (Christian M.), Duijts, L. (Liesbeth), Lie, R.T. (Rolv T.), Melton, P.E. (Phillip E.), Vonk, J.M. (Judith), Nohr, C. (Christian), Williams-DeVane, C. (ClarLynda), Huen, K. (Karen), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Gonseth, S. (Semira), Rezwan, F.I. (Faisal I.), Herceg, Z. (Zdenko), Ekström, S. (Sandra), Croen, L. (Lisa), Falahi, F. (Fahimeh), Perron, P. (Patrice), Karagas, M.R. (Margaret), Quraishi, B.M. (Bilal M.), Suderman, M.J. (Matthew J.), Magnus, M.C. (Maria C.), Jaddoe, V.W.V. (Vincent), Taylor, J.A. (Jack A.), Anderson, D. (Denise), Zhao, S. (Shanshan), Smit, H.A. (Henriëtte), Josey, M.J. (Michele J.), Bradman, A. (Asa), Baccarelli, A.A. (Andrea), Bustamante, M. (Mariona), Håberg, S.E. (Siri E), Pershagen, G. (Göran), Hertz-Picciotto, I. (Irva), Newschaffer, C. (Craig), Corpeleijn, W.E. (Willemijn), Bouchard, L. (Luigi), Lawlor, D.A. (Debbie A.), Maguire, R.L. (Rachel L.), Barcellos, L.F. (Lisa), Smith, G.D. (George Davey), Eskenazi, B. (B.), Karmaus, W. (Wilfried), Marsit, C.J. (Carmen J.), Hivert, M.-F. (Marie-France), Snieder, H. (Harold), Fallin, M.D. (M. Daniele), Melén, E. (Erik), Munthe-Kaas, M.C. (Monica Cheng), Arshad, H. (Hasan), Wiemels, J. (Joseph), Annesi-Maesano, I. (Isabella), Vrijheid, M. (Martine), Oken, E. (Emily), Holland, N. (Nina), Murphy, S.K. (Susan K.), Sørensen, T.I.A. (Thorkild), Koppelman, G.H. (Gerard), Newnham, J.P. (John), Wilcox, A.J. (Allen), Nystad, W. (Wenche), London, S.J. (Stephanie J.), Felix, J.F. (Janine), Relton, C.L. (Caroline), Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Poppelaars-Monnereau, C. (Claire), Allard, C. (Catherine), Yousefi, P. (Paul), Everson, T.M. (Todd M.), Bohlin, J. (Jon), Xu, Z. (Zongli), Huang, R.-C. (Rae-Chi), Reese, S.E. (Sarah E.), Xu, C.-J. (Cheng-Jian), Baïz, N. (Nour), Hoyo, C. (Cathrine), Agha, G. (Golareh), Roy, R. (Ritu), Holloway, J. (John), Ghantous, A. (Akram), Merid, S.K. (Simon Kebede), Bakulski, K.M. (Kelly M.), Küpers, A.M. (Marlijn), Zhang, H. (Hongmei), Richmond, R.C. (Rebecca C.), Page, C.M. (Christian M.), Duijts, L. (Liesbeth), Lie, R.T. (Rolv T.), Melton, P.E. (Phillip E.), Vonk, J.M. (Judith), Nohr, C. (Christian), Williams-DeVane, C. (ClarLynda), Huen, K. (Karen), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Gonseth, S. (Semira), Rezwan, F.I. (Faisal I.), Herceg, Z. (Zdenko), Ekström, S. (Sandra), Croen, L. (Lisa), Falahi, F. (Fahimeh), Perron, P. (Patrice), Karagas, M.R. (Margaret), Quraishi, B.M. (Bilal M.), Suderman, M.J. (Matthew J.), Magnus, M.C. (Maria C.), Jaddoe, V.W.V. (Vincent), Taylor, J.A. (Jack A.), Anderson, D. (Denise), Zhao, S. (Shanshan), Smit, H.A. (Henriëtte), Josey, M.J. (Michele J.), Bradman, A. (Asa), Baccarelli, A.A. (Andrea), Bustamante, M. (Mariona), Håberg, S.E. (Siri E), Pershagen, G. (Göran), Hertz-Picciotto, I. (Irva), Newschaffer, C. (Craig), Corpeleijn, W.E. (Willemijn), Bouchard, L. (Luigi), Lawlor, D.A. (Debbie A.), Maguire, R.L. (Rachel L.), Barcellos, L.F. (Lisa), Smith, G.D. (George Davey), Eskenazi, B. (B.), Karmaus, W. (Wilfried), Marsit, C.J. (Carmen J.), Hivert, M.-F. (Marie-France), Snieder, H. (Harold), Fallin, M.D. (M. Daniele), Melén, E. (Erik), Munthe-Kaas, M.C. (Monica Cheng), Arshad, H. (Hasan), Wiemels, J. (Joseph), Annesi-Maesano, I. (Isabella), Vrijheid, M. (Martine), Oken, E. (Emily), Holland, N. (Nina), Murphy, S.K. (Susan K.), Sørensen, T.I.A. (Thorkild), Koppelman, G.H. (Gerard), Newnham, J.P. (John), Wilcox, A.J. (Allen), Nystad, W. (Wenche), London, S.J. (Stephanie J.), Felix, J.F. (Janine), and Relton, C.L. (Caroline)

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 a6causal 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.

Published
2017
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9. Epigenetic Signatures of Cigarette Smoking

Author

Joehanes, R. (Roby), Just, A.C. (Allan C.), Marioni, R.E. (Riccardo), Pilling, L.C. (Luke), Reynolds, L.M. (Lindsay), Mandaviya, P.R. (Pooja R.), Guan, W. (Weihua), Xu, T. (Tao), Elks, C.E. (Cathy), Aslibekyan, S. (Stella), Moreno-Macías, H. (Hortensia), Smith, J.A. (Jennifer A), Brody, J.A. (Jennifer A.), Dhingra, R. (Radhika), Yousefi, P. (Paul), Pankow, J.S. (James), Kunze, S. (Sonja), Shah, S.H. (Sonia H.), McRae, A.F. (Allan F.), Lohman, K. (Kurt), Sha, J. (Jin), Absher, D. (Devin), Ferrucci, L. (Luigi), Zhao, W. (Wei), Demerath, E.W. (Ellen), Bressler, J. (Jan), Grove, M.L. (Megan), Huan, T. (Tianxiao), Liu, C. (Chunyu), Mendelson, M.M. (Michael M.), Yao, C. (Chen), Kiel, D.P. (Douglas P.), Peters, A. (Annette), Wang-Sattler, R. (Rui), Visscher, P.M. (Peter), Wray, N.R. (Naomi), Starr, J.M. (John), Ding, J. (Jingzhong), Rodriguez, C.J. (Carlos J.), Wareham, N.J. (Nick), Irvin, M.R. (Marguerite R.), Zhi, D. (Degui), Barrdahl, M. (Myrto), Vineis, P. (Paolo), Ambatipudi, S. (Srikant), Uitterlinden, A.G. (André), Hofman, A. (Albert), Schwartz, J. (Joel), Colicino, E. (Elena), Hou, L. (Lifang), Vokonas, P.S. (Pantel S.), Hernandez, D.G. (Dena), Singleton, A. (Andrew), Bandinelli, S. (Stefania), Turner, S.T. (Stephen), Ware, E.B. (Erin B.), Smith, A.K. (Alicia K.), Klengel, T. (Torsten), Binder, E.B. (Elisabeth B.), Psaty, B.M. (Bruce), Taylor, K.D. (Kent), Gharib, S.A. (Sina), Swenson, B.R. (Brenton R.), Liang, L. (Liming), Demeo, D.L. (Dawn), O'Connor, G.T. (George), Herceg, Z. (Zdenko), Ressler, K.J. (Kerry J.), Conneely, K.N. (Karen N.), Sotoodehnia, N. (Nona), Kardia, S.L.R. (Sharon L. R.), Melzer, D. (David), Baccarelli, A.A. (Andrea), Meurs, J.B.J. (Joyce) van, Romieu, I. (Isabelle), Arnett, D.K. (Donna), Ong, K.K. (Ken K.), Liu, Y. (YongMei), Waldenberger, M. (Melanie), Deary, I.J. (Ian), Fornage, M. (Myriam), Levy, D. (Daniel), London, S.J. (Stephanie J.), Joehanes, R. (Roby), Just, A.C. (Allan C.), Marioni, R.E. (Riccardo), Pilling, L.C. (Luke), Reynolds, L.M. (Lindsay), Mandaviya, P.R. (Pooja R.), Guan, W. (Weihua), Xu, T. (Tao), Elks, C.E. (Cathy), Aslibekyan, S. (Stella), Moreno-Macías, H. (Hortensia), Smith, J.A. (Jennifer A), Brody, J.A. (Jennifer A.), Dhingra, R. (Radhika), Yousefi, P. (Paul), Pankow, J.S. (James), Kunze, S. (Sonja), Shah, S.H. (Sonia H.), McRae, A.F. (Allan F.), Lohman, K. (Kurt), Sha, J. (Jin), Absher, D. (Devin), Ferrucci, L. (Luigi), Zhao, W. (Wei), Demerath, E.W. (Ellen), Bressler, J. (Jan), Grove, M.L. (Megan), Huan, T. (Tianxiao), Liu, C. (Chunyu), Mendelson, M.M. (Michael M.), Yao, C. (Chen), Kiel, D.P. (Douglas P.), Peters, A. (Annette), Wang-Sattler, R. (Rui), Visscher, P.M. (Peter), Wray, N.R. (Naomi), Starr, J.M. (John), Ding, J. (Jingzhong), Rodriguez, C.J. (Carlos J.), Wareham, N.J. (Nick), Irvin, M.R. (Marguerite R.), Zhi, D. (Degui), Barrdahl, M. (Myrto), Vineis, P. (Paolo), Ambatipudi, S. (Srikant), Uitterlinden, A.G. (André), Hofman, A. (Albert), Schwartz, J. (Joel), Colicino, E. (Elena), Hou, L. (Lifang), Vokonas, P.S. (Pantel S.), Hernandez, D.G. (Dena), Singleton, A. (Andrew), Bandinelli, S. (Stefania), Turner, S.T. (Stephen), Ware, E.B. (Erin B.), Smith, A.K. (Alicia K.), Klengel, T. (Torsten), Binder, E.B. (Elisabeth B.), Psaty, B.M. (Bruce), Taylor, K.D. (Kent), Gharib, S.A. (Sina), Swenson, B.R. (Brenton R.), Liang, L. (Liming), Demeo, D.L. (Dawn), O'Connor, G.T. (George), Herceg, Z. (Zdenko), Ressler, K.J. (Kerry J.), Conneely, K.N. (Karen N.), Sotoodehnia, N. (Nona), Kardia, S.L.R. (Sharon L. R.), Melzer, D. (David), Baccarelli, A.A. (Andrea), Meurs, J.B.J. (Joyce) van, Romieu, I. (Isabelle), Arnett, D.K. (Donna), Ong, K.K. (Ken K.), Liu, Y. (YongMei), Waldenberger, M. (Melanie), Deary, I.J. (Ian), Fornage, M. (Myriam), Levy, D. (Daniel), and London, S.J. (Stephanie J.)

Abstract

Background-DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results-To comprehensively determine the association between cigarette smoki

Published
2016
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10. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Author

Joubert, B.R. (Bonnie), Felix, J.F. (Janine), Yousefi, P. (Paul), Bakulski, K.M. (Kelly M.), Just, A.C. (Allan C.), Breton, C. (Carrie), Reese, S.E. (Sarah E.), Markunas, C.A. (Christina A.), Richmond, R.C. (Rebecca C.), Xu, C.-J. (Cheng-Jian), Küpers, L.K. (Leanne), Oh, S.S. (Sam S.), Hoyo, C. (Cathrine), Gruzieva, O. (Olena), Söderhäll, C. (Cilla), Salas, L.A. (Lucas A.), Baïz, N. (Nour), Zhang, H. (Hongmei), Lepeule, J. (Johanna), Ruiz, C. (Carlos), Ligthart, S. (Symen), Wang, T. (Tianyuan), Taylor, J.A. (Jack A.), Duijts, L. (Liesbeth), Sharp, G.C. (Gemma C.), Jankipersadsing, S.A. (Soesma A.), Nilsen, R.M. (Roy M.), Vaez, A. (Ahmad), Fallin, M.D. (M. Daniele), Hu, D. (Donglei), Litonjua, A.A. (Augusto), Fuemmeler, B.F. (Bernard F.), Huen, K. (Karen), Kere, J. (Juha), Kull, C.A. (Christian), Munthe-Kaas, M.C. (Monica Cheng), Gehring, U. (Ulrike), Bustamante, M. (Mariona), Saurel-Coubizolles, M.J. (Marie José), Quraishi, B.M. (Bilal M.), Ren, J. (Jie), Tost, J. (Jörg), Gonzalez, J.R. (Juan R.), Peters, M.J. (Marjolein), Håberg, S.E. (Siri E), Xu, Z. (Zongli), Meurs, J.B.J. (Joyce) van, Gaunt, T.R. (Tom), Kerkhof, M. (Marjan), Corpeleijn, W.E. (Willemijn), Feinberg, A.P. (Andrew P.), Eng, C. (Celeste), Baccarelli, A.A. (Andrea), Benjamin Neelon, S.E. (Sara E.), Bradman, A. (Asa), Merid, S.K. (Simon Kebede), Bergström, A. (Anna), Herceg, Z. (Zdenko), Hernandez-Vargas, H. (Hector), Brunekreef, B. (Bert), Pinart, M. (Mariona), Heude, B. (Barbara), Ewart, S. (Susan), Yao, J. (Jin), Lemonnier, N. (Nathanaël), Franco, O.H. (Oscar), Wu, M.C. (Michael), Hofman, A. (Albert), McArdle, W.L. (Wendy), Vlies, P. (P.) van der, Falahi, F. (Fahimeh), Gillman, M.W. (Matthew W.), Barcellos, L.F. (Lisa), Kumar, A. (Ashish), Wickman, M. (Magnus), Guerra, S. (S.), Charles, M.-A. (Marie-Aline), Holloway, J. (John), Auffray, C. (C.), Tiemeier, H.W. (Henning), Smith, A.V. (Davey), Postma, D.S. (Dirkje), Hivert, M.-F. (Marie-France), Eskenazi, B. (Brenda), Vrijheid, M. (Martine), Arshad, H. (Hasan), Anto, J.M. (Josep), Dehghan, A. (Abbas), Karmaus, W. (Wilfried), Annesi-Maesano, I. (Isabella), Sunyer, J. (Jordi), Ghantous, A. (Akram), Pershagen, G. (Göran), Holland, N. (Nina), Murphy, S.K. (Susan K.), Demeo, D.L. (Dawn), Burchard, E.G. (Esteban), Ladd-Acosta, C. (Christine), Snieder, H. (Harold), Nystad, W. (Wenche), Koppelman, G.H. (Gerard), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), Wilcox, A.J. (Allen), Melén, E. (Erik), London, S.J. (Stephanie J.), Joubert, B.R. (Bonnie), Felix, J.F. (Janine), Yousefi, P. (Paul), Bakulski, K.M. (Kelly M.), Just, A.C. (Allan C.), Breton, C. (Carrie), Reese, S.E. (Sarah E.), Markunas, C.A. (Christina A.), Richmond, R.C. (Rebecca C.), Xu, C.-J. (Cheng-Jian), Küpers, L.K. (Leanne), Oh, S.S. (Sam S.), Hoyo, C. (Cathrine), Gruzieva, O. (Olena), Söderhäll, C. (Cilla), Salas, L.A. (Lucas A.), Baïz, N. (Nour), Zhang, H. (Hongmei), Lepeule, J. (Johanna), Ruiz, C. (Carlos), Ligthart, S. (Symen), Wang, T. (Tianyuan), Taylor, J.A. (Jack A.), Duijts, L. (Liesbeth), Sharp, G.C. (Gemma C.), Jankipersadsing, S.A. (Soesma A.), Nilsen, R.M. (Roy M.), Vaez, A. (Ahmad), Fallin, M.D. (M. Daniele), Hu, D. (Donglei), Litonjua, A.A. (Augusto), Fuemmeler, B.F. (Bernard F.), Huen, K. (Karen), Kere, J. (Juha), Kull, C.A. (Christian), Munthe-Kaas, M.C. (Monica Cheng), Gehring, U. (Ulrike), Bustamante, M. (Mariona), Saurel-Coubizolles, M.J. (Marie José), Quraishi, B.M. (Bilal M.), Ren, J. (Jie), Tost, J. (Jörg), Gonzalez, J.R. (Juan R.), Peters, M.J. (Marjolein), Håberg, S.E. (Siri E), Xu, Z. (Zongli), Meurs, J.B.J. (Joyce) van, Gaunt, T.R. (Tom), Kerkhof, M. (Marjan), Corpeleijn, W.E. (Willemijn), Feinberg, A.P. (Andrew P.), Eng, C. (Celeste), Baccarelli, A.A. (Andrea), Benjamin Neelon, S.E. (Sara E.), Bradman, A. (Asa), Merid, S.K. (Simon Kebede), Bergström, A. (Anna), Herceg, Z. (Zdenko), Hernandez-Vargas, H. (Hector), Brunekreef, B. (Bert), Pinart, M. (Mariona), Heude, B. (Barbara), Ewart, S. (Susan), Yao, J. (Jin), Lemonnier, N. (Nathanaël), Franco, O.H. (Oscar), Wu, M.C. (Michael), Hofman, A. (Albert), McArdle, W.L. (Wendy), Vlies, P. (P.) van der, Falahi, F. (Fahimeh), Gillman, M.W. (Matthew W.), Barcellos, L.F. (Lisa), Kumar, A. (Ashish), Wickman, M. (Magnus), Guerra, S. (S.), Charles, M.-A. (Marie-Aline), Holloway, J. (John), Auffray, C. (C.), Tiemeier, H.W. (Henning), Smith, A.V. (Davey), Postma, D.S. (Dirkje), Hivert, M.-F. (Marie-France), Eskenazi, B. (Brenda), Vrijheid, M. (Martine), Arshad, H. (Hasan), Anto, J.M. (Josep), Dehghan, A. (Abbas), Karmaus, W. (Wilfried), Annesi-Maesano, I. (Isabella), Sunyer, J. (Jordi), Ghantous, A. (Akram), Pershagen, G. (Göran), Holland, N. (Nina), Murphy, S.K. (Susan K.), Demeo, D.L. (Dawn), Burchard, E.G. (Esteban), Ladd-Acosta, C. (Christine), Snieder, H. (Harold), Nystad, W. (Wenche), Koppelman, G.H. (Gerard), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), Wilcox, A.J. (Allen), Melén, E. (Erik), and London, S.J. (Stephanie J.)

Abstract

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathwa

Published
2016
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