Search

Your search keyword '"Corpeleijn, E. (Eva)"' showing total 13 results
Start Over Author "Corpeleijn, E. (Eva)"
13 results on '"Corpeleijn, E. (Eva)"'

1. Cohort description:measures of early-life behaviour and later psychopathology in the LifeCycle Project — EU Child Cohort Network

Author

Nader, J. L. (Johanna L.), López-Vicente, M. (Mònica), Julvez, J. (Jordi), Guxens, M. (Monica), Cadman, T. (Tim), Elhakeem, A. (Ahmed), Järvelin, M.-R. (Marjo-Riitta), Rautio, N. (Nina), Miettunen, J. (Jouko), El Marroun, H. (Hanan), Melchior, M. (Maria), Heude, B. (Barbara), Charles, M.-A. (Marie-Aline), Yang, T. C. (Tiffany C.), McEachan, R. R. (Rosemary R. C.), Wright, J. (John), Polanska, K. (Kinga), Carson, J. (Jennie), Lin, A. (Ashleigh), Rauschert, S. (Sebastian), Huang, R.-C. (Rae-Chi), Popovic, M. (Maja), Richiardi, L. (Lorenzo), Corpeleijn, E. (Eva), Cardol, M. (Marloes), Mikkola, T. M. (Tuija M.), Eriksson, J. G. (Johan G.), Salika, T. (Theodosia), Inskip, H. (Hazel), Vinther, J. L. (Johan Lerbech), Strandberg-Larsen, K. (Katrine), Gürlich, K. (Kathrin), Grote, V. (Veit), Koletzko, B. (Berthold), Vafeiadi, M. (Marina), Sunyer, J. (Jordi), Jaddoe, V. W. (Vincent W. V.), Harris, J. R. (Jennifer R.), Nader, J. L. (Johanna L.), López-Vicente, M. (Mònica), Julvez, J. (Jordi), Guxens, M. (Monica), Cadman, T. (Tim), Elhakeem, A. (Ahmed), Järvelin, M.-R. (Marjo-Riitta), Rautio, N. (Nina), Miettunen, J. (Jouko), El Marroun, H. (Hanan), Melchior, M. (Maria), Heude, B. (Barbara), Charles, M.-A. (Marie-Aline), Yang, T. C. (Tiffany C.), McEachan, R. R. (Rosemary R. C.), Wright, J. (John), Polanska, K. (Kinga), Carson, J. (Jennie), Lin, A. (Ashleigh), Rauschert, S. (Sebastian), Huang, R.-C. (Rae-Chi), Popovic, M. (Maja), Richiardi, L. (Lorenzo), Corpeleijn, E. (Eva), Cardol, M. (Marloes), Mikkola, T. M. (Tuija M.), Eriksson, J. G. (Johan G.), Salika, T. (Theodosia), Inskip, H. (Hazel), Vinther, J. L. (Johan Lerbech), Strandberg-Larsen, K. (Katrine), Gürlich, K. (Kathrin), Grote, V. (Veit), Koletzko, B. (Berthold), Vafeiadi, M. (Marina), Sunyer, J. (Jordi), Jaddoe, V. W. (Vincent W. V.), and Harris, J. R. (Jennifer R.)

Abstract

Background: The EU LifeCycle Project was launched in 2017 to combine, harmonise, and analyse data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview over the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. Methods: Data on cognitive, behavioural and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data for ages 0–18+ years, covering domains across a wide range of behavioural and psychopathology indicators and outcomes (including executive function, depression, ADHD and cognition). These data span a unique combination of qualitative data collected through behavioural/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of brain imaging (MRI, foetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. Conclusions: Mental health data harmonized through the LifeCycle project can be used to study life course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Published
2023

2. DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

Author

Dongen, J. (Jenny) van, Hagenbeek, F.A. (Fiona A.), Suderman, M.J. (Matthew J.), Roetman, P.J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A.G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R.H. (Rosa), Hafferty, J.D. (Jonathan D.), Adams, M.J. (Mark J.), Walker, R.M. (Rosie M.), Morris, S.W. (Stewart W.), Lahti, J. (Jari), Küpers, A.M. (Marlijn), Escaramis, G. (Georgia), Alemany, S. (Silvia), Jan Bonder, M. (Marc), Meijer, M. (Mandy), Ip, H.F. (Hill F.), Jansen, R. (Rick), Baselmans, B.M.L. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T.S. (Tabea S.), Frank, J. (Josef), Jylhävä, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P.P. (Pashupati Prasad), Colins, O.F. (Olivier F.), Corcoran, D.L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J.F. (Janine), Bakermans-Kranenburg, M.J. (Marian), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J.R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K.B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G.E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Järvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C.M. (Christine), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernández-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Vermeiren, R.R.J.M. (Robert R.J.M.), Strandberg, T. (Timo), Räikkönen, K. (Katri), Snieder, H. (Harold), Witt, S.H. (Stephanie H), Deuschle, M. (Michael), Pedersen, N.L. (Nancy), Hägg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T.E. (Terrie E.), Tiemeier, H.W. (Henning), IJzendoorn, M.H. (Rien) van, Relton, C.L. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K.L. (Kathryn L.), McIntosh, A.M. (Andrew), Bartels, M. (Meike), Boomsma, D.I. (Dorret I.), Dongen, J. (Jenny) van, Hagenbeek, F.A. (Fiona A.), Suderman, M.J. (Matthew J.), Roetman, P.J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A.G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R.H. (Rosa), Hafferty, J.D. (Jonathan D.), Adams, M.J. (Mark J.), Walker, R.M. (Rosie M.), Morris, S.W. (Stewart W.), Lahti, J. (Jari), Küpers, A.M. (Marlijn), Escaramis, G. (Georgia), Alemany, S. (Silvia), Jan Bonder, M. (Marc), Meijer, M. (Mandy), Ip, H.F. (Hill F.), Jansen, R. (Rick), Baselmans, B.M.L. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T.S. (Tabea S.), Frank, J. (Josef), Jylhävä, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P.P. (Pashupati Prasad), Colins, O.F. (Olivier F.), Corcoran, D.L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J.F. (Janine), Bakermans-Kranenburg, M.J. (Marian), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J.R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K.B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G.E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Järvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C.M. (Christine), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernández-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimäki, T. (Terho), Vermeiren, R.R.J.M. (Robert R.J.M.), Strandberg, T. (Timo), Räikkönen, K. (Katri), Snieder, H. (Harold), Witt, S.H. (Stephanie H), Deuschle, M. (Michael), Pedersen, N.L. (Nancy), Hägg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T.E. (Terrie E.), Tiemeier, H.W. (Henning), IJzendoorn, M.H. (Rien) van, Relton, C.L. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Jarvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K.L. (Kathryn L.), McIntosh, A.M. (Andrew), Bartels, M. (Meike), and Boomsma, D.I. (Dorret I.)

Abstract

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48

Published
2021
Full Text
View/download PDF

3. DNA methylation signatures of aggression and closely related constructs:a meta-analysis of epigenome-wide studies across the lifespan

Author

van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), Boomsma, D. I. (Dorret, I), van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), and Boomsma, D. I. (Dorret, I)

Abstract

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

Published
2021

4. The EU Child Cohort Network’s core data:establishing a set of findable, accessible, interoperable and re-usable (FAIR) variables

Author

Pinot de Moira, A. (Angela), Haakma, S. (Sido), Strandberg-Larsen, K. (Katrine), van Enckevort, E. (Esther), Kooijman, M. (Marjolein), Cadman, T. (Tim), Cardol, M. (Marloes), Corpeleijn, E. (Eva), Crozier, S. (Sarah), Duijts, L. (Liesbeth), Elhakeem, A. (Ahmed), Eriksson, J. G. (Johan G.), Felix, J. F. (Janine F.), Fernandez-Barres, S. (Silvia), Foong, R. E. (Rachel E.), Forhan, A. (Anne), Grote, V. (Veit), Guerlich, K. (Kathrin), Heude, B. (Barbara), Huang, R.-C. (Rae-Chi), Järvelin, M.-R. (Marjo-Riitta), Jorgensen, A. C. (Anne Cathrine), Mikkola, T. M. (Tuija M.), Nader, J. L. (Johanna L. T.), Pedersen, M. (Marie), Popovic, M. (Maja), Rautio, N. (Nina), Richiardi, L. (Lorenzo), Ronkainen, J. (Justiina), Roumeliotaki, T. (Theano), Salika, T. (Theodosia), Sebert, S. (Sylvain), Vinther, J. L. (Johan L.), Voerman, E. (Ellis), Vrijheid, M. (Martine), Wright, J. (John), Yang, T. C. (Tiffany C.), Zariouh, F. (Faryal), Charles, M.-A. (Marie-Aline), Inskip, H. (Hazel), Jaddoe, V. W. (Vincent W. V.), Swertz, M. A. (Morris A.), Nybo Andersen, A.-M. (Anne-Marie), Pinot de Moira, A. (Angela), Haakma, S. (Sido), Strandberg-Larsen, K. (Katrine), van Enckevort, E. (Esther), Kooijman, M. (Marjolein), Cadman, T. (Tim), Cardol, M. (Marloes), Corpeleijn, E. (Eva), Crozier, S. (Sarah), Duijts, L. (Liesbeth), Elhakeem, A. (Ahmed), Eriksson, J. G. (Johan G.), Felix, J. F. (Janine F.), Fernandez-Barres, S. (Silvia), Foong, R. E. (Rachel E.), Forhan, A. (Anne), Grote, V. (Veit), Guerlich, K. (Kathrin), Heude, B. (Barbara), Huang, R.-C. (Rae-Chi), Järvelin, M.-R. (Marjo-Riitta), Jorgensen, A. C. (Anne Cathrine), Mikkola, T. M. (Tuija M.), Nader, J. L. (Johanna L. T.), Pedersen, M. (Marie), Popovic, M. (Maja), Rautio, N. (Nina), Richiardi, L. (Lorenzo), Ronkainen, J. (Justiina), Roumeliotaki, T. (Theano), Salika, T. (Theodosia), Sebert, S. (Sylvain), Vinther, J. L. (Johan L.), Voerman, E. (Ellis), Vrijheid, M. (Martine), Wright, J. (John), Yang, T. C. (Tiffany C.), Zariouh, F. (Faryal), Charles, M.-A. (Marie-Aline), Inskip, H. (Hazel), Jaddoe, V. W. (Vincent W. V.), Swertz, M. A. (Morris A.), and Nybo Andersen, A.-M. (Anne-Marie)

Abstract

The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network’s core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network’s data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community.

Published
2021

5. 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
Full Text
View/download PDF

6. The LifeCycle Project-EU Child Cohort Network: a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Author

Jaddoe, V.W.V. (Vincent), Felix, J.F. (Janine), Andersen, A-M.N. (Anne-Marie Nybo), Charles, M.A., Chatzi, L. (Leda), Corpeleijn, E. (Eva), Donner, N. (Nina), Elhakeem, A. (Ahmed), Hagen, K. (Knut), Foong, R. (Rachel), Grote, V. (Veit), Haakma, S. (Sido), Hanson, M. (Mark), Harris, J.R. (Jennifer), Heude, B. (Barbara), Huang, R.-C. (Rae-Chi), Inskip, H.M. (Hazel), Järvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Lawlor, D.A. (Debbie), Lindeboom, M. (Maarten), McEachan, R.R.C. (Rosemary R. C.), Mikkola, T.M. (Tuija M.), Nader, J.L.T. (Johanna L. T.), de Moira, A.P. (Angela Pinot), Pizzi, C. (Costanza), Richiardi, L. (Lorenzo), Sebert, S. (Sylvain), Schwalber, A. (Ameli), Sunyer, J. (Jordi), Swertz, M.A. (Morris A.), Vafeiadi, M. (Marina), Vrijheid, M. (Martine), Wright, J. (John), Duijts, L. (Liesbeth), El Marroun, H. (Hanan), Gaillard, R. (Romy), Santos, S. (Susana), Geurtsen, M.L. (Madelon L.), Kooijman, M.N. (Marjolein), Mensink-Bout, S.M. (Sara M.), Vehmeijer, F.O.L. (Florianne O.L.), Voerman, E. (Ellis), Nieuwenhuijsen, M. (Mark), Basagaña, X. (Xavier), Bustamante, M. (Mariona), Casas, M. (Miguel), de Castro, M. (Montserrat), Cirugeda, L.E. (Lourdes E.), Fernández-Barrés, S., Fossati, S. (Serena), Garcia, R. (Raquel), Julvez, J. (Jordi), Lertxundi, A. (Aitana), Lertxundi, N. (Nerea), Llop, S. (Sabrina), López-Vicente, M. (Mònica), Lopez-Espinosa, M.-J. (Maria-Jose), Maitre, L. (Lea), Murcia, M. (Mario), Lea, J. (Jose), Urquiza, H. (H.), Warembourg, C. (Charline), Zugna, D. (Daniela), Popovic, M. (Maja), Isaevska, E. (Elena), Maule, M. (Milena), Moccia, C. (Chiara), Moirano, G. (Giovenale), Rasella, D. (Davide), Hanson, M.A. (Mark A.), Inskip, H.M. (Hazel M.), Jacob, C.M. (Chandni Maria), Salika, T. (Theodosia), Cadman, T. (Tim), Strandberg-Larsen, K.M. (Katrine M.), Pedersen, M. (Marie), Vinther, J.L. (Johan L.), Wilson, P. (Paul), Mason, D. (Dan), Yang, T.C. (Tiffany C.), Cardol, M. (Marloes), van Enckevoort, E. (Esther), Hyde, E. (Eleanor), Scholtens, S. (Salome), Snieder, H. (Harold), Thio, C.H.L. (Chris H. L.), Chatzi, L. (Lida), Margetaki, K.C.A. (Katerina C. A.), Roumeliotaki, T. (Theano), Nader, J.L. (Johanna L.), Knudsen, G.P. (Gun Peggy), Magnus, P. (Per), Panico, L. (Lidia), Ichou, M. (Mathieu), de Lauzon-Guillain, B. (Blandine), Dargent-Molina, P. (Patricia), Cornet, M. (Maxime), Florian, S.M. (Sandra M.), Harrar, F. (Faryal), Lepeule, J. (Johanna), Lioret, S., Melchior, M. (Maria), Plancoulaine, S. (Sabine), Männikkö, M. (Minna), Parmar, P. (Priyanka), Rautio, N. (Nina), Ronkainen, J. (Justiina), Tolvanen, M. (Mimmi), Aumüller, N. (Nicole), Closa-Monasterolo, R. (Ricardo), Escribano, J. (Joaquin), Ferré, N. (Natalia), Gruszfeld, D. (Dariusz), Gürlich, K. (Kathrin), Langhendries, J.P. (Jean Paul), Luque, V. (Verónica), Riva, E. (Enrica), Schwarzfischer, P. (Phillipp), Totzauer, M. (Martina), Verduci, E. (Elvira), Xhonneux, A. (Annick), Zaragoza-Jordana, M. (Marta), Schwalber, A. (Amelie), Foong, R.E. (Rachel E.), Hall, G.L. (Graham L.), Lin, A. (Ashleigh), Carson, J. (Jennie), Melton, P. (Phillip), Rauschert, S. (Sebastian), Jaddoe, V.W.V. (Vincent), Felix, J.F. (Janine), Andersen, A-M.N. (Anne-Marie Nybo), Charles, M.A., Chatzi, L. (Leda), Corpeleijn, E. (Eva), Donner, N. (Nina), Elhakeem, A. (Ahmed), Hagen, K. (Knut), Foong, R. (Rachel), Grote, V. (Veit), Haakma, S. (Sido), Hanson, M. (Mark), Harris, J.R. (Jennifer), Heude, B. (Barbara), Huang, R.-C. (Rae-Chi), Inskip, H.M. (Hazel), Järvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Lawlor, D.A. (Debbie), Lindeboom, M. (Maarten), McEachan, R.R.C. (Rosemary R. C.), Mikkola, T.M. (Tuija M.), Nader, J.L.T. (Johanna L. T.), de Moira, A.P. (Angela Pinot), Pizzi, C. (Costanza), Richiardi, L. (Lorenzo), Sebert, S. (Sylvain), Schwalber, A. (Ameli), Sunyer, J. (Jordi), Swertz, M.A. (Morris A.), Vafeiadi, M. (Marina), Vrijheid, M. (Martine), Wright, J. (John), Duijts, L. (Liesbeth), El Marroun, H. (Hanan), Gaillard, R. (Romy), Santos, S. (Susana), Geurtsen, M.L. (Madelon L.), Kooijman, M.N. (Marjolein), Mensink-Bout, S.M. (Sara M.), Vehmeijer, F.O.L. (Florianne O.L.), Voerman, E. (Ellis), Nieuwenhuijsen, M. (Mark), Basagaña, X. (Xavier), Bustamante, M. (Mariona), Casas, M. (Miguel), de Castro, M. (Montserrat), Cirugeda, L.E. (Lourdes E.), Fernández-Barrés, S., Fossati, S. (Serena), Garcia, R. (Raquel), Julvez, J. (Jordi), Lertxundi, A. (Aitana), Lertxundi, N. (Nerea), Llop, S. (Sabrina), López-Vicente, M. (Mònica), Lopez-Espinosa, M.-J. (Maria-Jose), Maitre, L. (Lea), Murcia, M. (Mario), Lea, J. (Jose), Urquiza, H. (H.), Warembourg, C. (Charline), Zugna, D. (Daniela), Popovic, M. (Maja), Isaevska, E. (Elena), Maule, M. (Milena), Moccia, C. (Chiara), Moirano, G. (Giovenale), Rasella, D. (Davide), Hanson, M.A. (Mark A.), Inskip, H.M. (Hazel M.), Jacob, C.M. (Chandni Maria), Salika, T. (Theodosia), Cadman, T. (Tim), Strandberg-Larsen, K.M. (Katrine M.), Pedersen, M. (Marie), Vinther, J.L. (Johan L.), Wilson, P. (Paul), Mason, D. (Dan), Yang, T.C. (Tiffany C.), Cardol, M. (Marloes), van Enckevoort, E. (Esther), Hyde, E. (Eleanor), Scholtens, S. (Salome), Snieder, H. (Harold), Thio, C.H.L. (Chris H. L.), Chatzi, L. (Lida), Margetaki, K.C.A. (Katerina C. A.), Roumeliotaki, T. (Theano), Nader, J.L. (Johanna L.), Knudsen, G.P. (Gun Peggy), Magnus, P. (Per), Panico, L. (Lidia), Ichou, M. (Mathieu), de Lauzon-Guillain, B. (Blandine), Dargent-Molina, P. (Patricia), Cornet, M. (Maxime), Florian, S.M. (Sandra M.), Harrar, F. (Faryal), Lepeule, J. (Johanna), Lioret, S., Melchior, M. (Maria), Plancoulaine, S. (Sabine), Männikkö, M. (Minna), Parmar, P. (Priyanka), Rautio, N. (Nina), Ronkainen, J. (Justiina), Tolvanen, M. (Mimmi), Aumüller, N. (Nicole), Closa-Monasterolo, R. (Ricardo), Escribano, J. (Joaquin), Ferré, N. (Natalia), Gruszfeld, D. (Dariusz), Gürlich, K. (Kathrin), Langhendries, J.P. (Jean Paul), Luque, V. (Verónica), Riva, E. (Enrica), Schwarzfischer, P. (Phillipp), Totzauer, M. (Martina), Verduci, E. (Elvira), Xhonneux, A. (Annick), Zaragoza-Jordana, M. (Marta), Schwalber, A. (Amelie), Foong, R.E. (Rachel E.), Hall, G.L. (Graham L.), Lin, A. (Ashleigh), Carson, J. (Jennie), Melton, P. (Phillip), and Rauschert, S. (Sebastian)

Abstract

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform

Published
2020
Full Text
View/download PDF

7. Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Author

Merid, S.K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G.C. (Gemma C.), Küpers, A.M. (Marlijn), Kho, A.T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F.O.L. (Florianne O.L.), Kazmi, N. (Nabila), Salas, L.A. (Lucas A.), Rezwan, F.I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S.L. (Sheryl), Melton, P.E. (Phillip E.), Lawlor, D.A. (Debbie A.), Pershagen, G. (Göran), Breton, C. (Carrie), Huen, K. (Karen), Baïz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T.S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, C. (Christian), Bustamante, M. (Mariona), Ewart, S. (Susan), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C.M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A.A. (Andrea), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C.L. (Caroline), Bergström, A. (Anna), Eskenazi, B. (B.), Soomro, M.H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Vrijheid, M. (Martine), Arshad, S.H. (Syed), Holloway, J.W. (John W.), Håberg, S.E. (Siri E), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E.B. (Elisabeth), Demeo, D.L. (Dawn), Vonk, J.M. (Judith), Newnham, J.P. (John), Tantisira, K.G. (Kelan G.), Kull, C.A. (Christian), Wiemels, J. (Joseph), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M.C. (Monica Cheng), Räikkönen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S.T. (Scott T.), Antó, J.M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Söderhäll, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S.E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Melén, E. (Erik), Merid, S.K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G.C. (Gemma C.), Küpers, A.M. (Marlijn), Kho, A.T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F.O.L. (Florianne O.L.), Kazmi, N. (Nabila), Salas, L.A. (Lucas A.), Rezwan, F.I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S.L. (Sheryl), Melton, P.E. (Phillip E.), Lawlor, D.A. (Debbie A.), Pershagen, G. (Göran), Breton, C. (Carrie), Huen, K. (Karen), Baïz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T.S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, C. (Christian), Bustamante, M. (Mariona), Ewart, S. (Susan), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C.M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A.A. (Andrea), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C.L. (Caroline), Bergström, A. (Anna), Eskenazi, B. (B.), Soomro, M.H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Vrijheid, M. (Martine), Arshad, S.H. (Syed), Holloway, J.W. (John W.), Håberg, S.E. (Siri E), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E.B. (Elisabeth), Demeo, D.L. (Dawn), Vonk, J.M. (Judith), Newnham, J.P. (John), Tantisira, K.G. (Kelan G.), Kull, C.A. (Christian), Wiemels, J. (Joseph), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M.C. (Monica Cheng), Räikkönen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S.T. (Scott T.), Antó, J.M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Söderhäll, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S.E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), and Melén, E. (Erik)

Abstract

BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

Published
2020
Full Text
View/download PDF

8. 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

9. Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Author

Merid, S. K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G. C. (Gemma C.), Kupers, L. K. (Leanne K.), Kho, A. T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F. O. (Florianne O.), Kazmi, N. (Nabila), Salas, L. A. (Lucas A.), Rezwan, F. I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S. L. (Sheryl L.), Melton, P. E. (Phillip E.), Lawlor, D. A. (Debbie A.), Pershagen, G. (Goran), Breton, C. V. (Carrie V.), Huen, K. (Karen), Baiz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T. S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, E. A. (Ellen Aagaard), Bustamante, M. (Mariona), Ewart, S. L. (Susan L.), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C. M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A. A. (Andrea A.), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C. L. (Caroline L.), Bergstrom, A. (Anna), Eskenazi, B. (Brenda), Soomro, M. H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V. W. (Vincent W.), Sorensen, T. I. (Thorkild I. A.), Vrijheid, M. (Martine), Arshad, S. H. (S. Hasan), Holloway, J. W. (John W.), Haberg, S. E. (Siri E.), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E. B. (Elisabeth B.), DeMeo, D. L. (Dawn L.), Vonk, J. M. (Judith M.), Newnham, J. (John), Tantisira, K. G. (Kelan G.), Kull, I. (Inger), Wiemels, J. L. (Joseph L.), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M. C. (Monica C.), Raikkonen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S. T. (Scott T.), Anto, J. M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Soderhall, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S. E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J. F. (Janine F.), Koppelman, G. H. (Gerard H.), London, S. J. (Stephanie J.), Melen, E. (Erik), Merid, S. K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G. C. (Gemma C.), Kupers, L. K. (Leanne K.), Kho, A. T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F. O. (Florianne O.), Kazmi, N. (Nabila), Salas, L. A. (Lucas A.), Rezwan, F. I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S. L. (Sheryl L.), Melton, P. E. (Phillip E.), Lawlor, D. A. (Debbie A.), Pershagen, G. (Goran), Breton, C. V. (Carrie V.), Huen, K. (Karen), Baiz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T. S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, E. A. (Ellen Aagaard), Bustamante, M. (Mariona), Ewart, S. L. (Susan L.), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C. M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A. A. (Andrea A.), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C. L. (Caroline L.), Bergstrom, A. (Anna), Eskenazi, B. (Brenda), Soomro, M. H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V. W. (Vincent W.), Sorensen, T. I. (Thorkild I. A.), Vrijheid, M. (Martine), Arshad, S. H. (S. Hasan), Holloway, J. W. (John W.), Haberg, S. E. (Siri E.), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E. B. (Elisabeth B.), DeMeo, D. L. (Dawn L.), Vonk, J. M. (Judith M.), Newnham, J. (John), Tantisira, K. G. (Kelan G.), Kull, I. (Inger), Wiemels, J. L. (Joseph L.), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M. C. (Monica C.), Raikkonen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S. T. (Scott T.), Anto, J. M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Soderhall, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S. E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J. F. (Janine F.), Koppelman, G. H. (Gerard H.), London, S. J. (Stephanie J.), and Melen, E. (Erik)

Abstract

Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P < 1.06 × 10⁻⁷, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

Published
2020

10. The LifeCycle Project-EU Child Cohort Network:a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Author

Jaddoe, V. W. (Vincent W. V.), Felix, J. F. (Janine F.), Andersen, A. N. (Anne‑Marie Nybo), Charles, M. (Marie‑Aline), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Donner, N. (Nina), Elhakeem, A. (Ahmed), Eriksson, J. G. (Johan G.), Foong, R. (Rachel), Grote, V. (Veit), Haakma, S. (Sido), Hanson, M. (Mark), Harris, J. R. (Jennifer R.), Heude, B. (Barbara), Huang, R. (Rae‑Chi), Inskip, H. (Hazel), Järvelin, M. (Marjo‑Riitta), Koletzko, B. (Berthold), Lawlor, D. A. (Deborah A.), Lindeboom, M. (Maarten), McEachan, R. R. (Rosemary R. C.), Mikkola, T. M. (Tuija M.), Nader, J. L. (Johanna L. T.), Pinot de Moira, A. (Angela), Pizzi, C. (Costanza), Richiardi, L. (Lorenzo), Sebert, S. (Sylvain), Schwalber, A. (Ameli), Sunyer, J. (Jordi), Swertz, M. A. (Morris A.), Vafeiadi, M. (Marina), Vrijheid, M. (Martine), Wright, J. (John), Duijts, L. (Liesbeth), L. P. (LifeCycle Project Group), Jaddoe, V. W. (Vincent W. V.), Felix, J. F. (Janine F.), Andersen, A. N. (Anne‑Marie Nybo), Charles, M. (Marie‑Aline), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Donner, N. (Nina), Elhakeem, A. (Ahmed), Eriksson, J. G. (Johan G.), Foong, R. (Rachel), Grote, V. (Veit), Haakma, S. (Sido), Hanson, M. (Mark), Harris, J. R. (Jennifer R.), Heude, B. (Barbara), Huang, R. (Rae‑Chi), Inskip, H. (Hazel), Järvelin, M. (Marjo‑Riitta), Koletzko, B. (Berthold), Lawlor, D. A. (Deborah A.), Lindeboom, M. (Maarten), McEachan, R. R. (Rosemary R. C.), Mikkola, T. M. (Tuija M.), Nader, J. L. (Johanna L. T.), Pinot de Moira, A. (Angela), Pizzi, C. (Costanza), Richiardi, L. (Lorenzo), Sebert, S. (Sylvain), Schwalber, A. (Ameli), Sunyer, J. (Jordi), Swertz, M. A. (Morris A.), Vafeiadi, M. (Marina), Vrijheid, M. (Martine), Wright, J. (John), Duijts, L. (Liesbeth), and L. P. (LifeCycle Project Group)

Abstract

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It

Published
2020

11. Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Author

Reese, S. E. (Sarah E.), Xu, C.-J. (Cheng-Jian), den Dekker, H. T. (Herman T.), Lee, M. K. (Mi Kyeong), Sikdar, S. (Sinjini), Ruiz-Arenas, C. (Carlos), Merid, S. K. (Simon K.), Rezwan, F. I. (Faisal I.), Page, C. M. (Christian M.), Ullemar, V. (Vilhelmina), Melton, P. E. (Phillip E.), Oh, S. S. (Sam S.), Yang, I. V. (Ivana V.), Burrows, K. (Kimberley), Söderhäll, C. (Cilla), Jima, D. D. (Dereje D.), Gao, L. (Lu), Arathimos, R. (Ryan), Küpers, L. K. (Leanne K.), Wielscher, M. (Matthias), Rzehak, P. (Peter), Lahti, J. (Jari), Laprise, C. (Catherine), Madore, A.-M. (Anne-Marie), Ward, J. (James), Bennett, B. D. (Brian D.), Wang, T. (Tianyuan), Bell, D. A. (Douglas A.), T. B. (The BIOS consortium), Vonk, J. M. (Judith M.), Håberg, S. E. (Siri E.), Zhao, S. (Shanshan), Karlsson, R. (Robert), Hollams, E. (Elysia), Hu, D. (Donglei), Richards, A. J. (Adam J.), Bergström, A. (Anna), Sharp, G. C. (Gemma C.), Felix, J. F. (Janine F.), Bustamante, M. (Mariona), Gruzieva, O. (Olena), Maguire, R. L. (Rachel L.), Gilliland, F. (Frank), Baïz, N. (Nour), Nohr, E. A. (Ellen A.), Corpeleijn, E. (Eva), Sebert, S. (Sylvain), Karmaus, W. (Wilfried), Grote, V. (Veit), Kajantie, E. (Eero), Magnus, M. C. (Maria C.), Örtqvist, A. K. (Anne K.), Eng, C. (Celeste), Liu, A. H. (Andrew H.), Kull, I. (Inger), Jaddoe, V. W. (Vincent W.V.), Sunyer, J. (Jordi), Kere, J. (Juha), Hoyo, C. (Cathrine), Annesi-Maesano, I. (Isabella), Arshad, S. H. (Syed Hasan), Koletzko, B. (Berthold), Brunekreef, B. (Bert), Binder, E. B. (Elisabeth B.), Räikkönen, K. (Katri), Reischl, E. (Eva), Holloway, J. W. (John W.), Järvelin, M.-R. (Marjo-Riitta), Snieder, H. (Harold), Kazmi, N. (Nabila), Breton, C. V. (Carrie V.), Murphy, S. K. (Susan K.), Pershagen, G. (Göran), Anto, J. M. (Josep Maria), Relton, C. L. (Caroline L.), Schwartz, D. A. (David A.), Burchard, E. G. (Esteban G.), Huang, R.-C. (Rae-Chi), Nystad, W. (Wenche), Almqvist, C. (Catarina), Henderson, A. J. (A. John), Melén, E. (Erik), Duijts, L. (Liesbeth), Koppelman, G. H. (Gerard H.), and London, S. J. (Stephanie J.)

Subjects
epigenetics, newborn, methylation, asthma, drug development, childhood
Abstract

Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. Methods: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. Results: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. Conclusion: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.

Published
2019

12. 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

13. 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

Catalog

Books, media, physical & digital resources
See catalog results