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2. A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Author

Li, Shaobo, Spitz, Natalia, Ghantous, Akram, Abrishamcar, Sarina, Reimann, Brigitte, Marques, Irene, Silver, Matt J, Aguilar-Lacasaña, Sofía, Kitaba, Negusse, Rezwan, Faisal I, Röder, Stefan, Sirignano, Lea, Tuhkanen, Johanna, Mancano, Giulia, Sharp, Gemma C, Metayer, Catherine, Morimoto, Libby, Stein, Dan J, Zar, Heather J, Alfano, Rossella, Nawrot, Tim, Wang, Congrong, Kajantie, Eero, Keikkala, Elina, Mustaniemi, Sanna, Ronkainen, Justiina, Sebert, Sylvain, Silva, Wnurinham, Vääräsmäki, Marja, Jaddoe, Vincent WV, Bernstein, Robin M, Prentice, Andrew M, Cosin-Tomas, Marta, Dwyer, Terence, Håberg, Siri Eldevik, Herceg, Zdenko, Magnus, Maria C, Munthe-Kaas, Monica Cheng, Page, Christian M, Völker, Maja, Gilles, Maria, Send, Tabea, Witt, Stephanie, Zillich, Lea, Gagliardi, Luigi, Richiardi, Lorenzo, Czamara, Darina, Räikkönen, Katri, Chatzi, Lida, Vafeiadi, Marina, Arshad, S Hasan, Ewart, Susan, Plusquin, Michelle, Felix, Janine F, Moore, Sophie E, Vrijheid, Martine, Holloway, John W, Karmaus, Wilfried, Herberth, Gunda, Zenclussen, Ana, Streit, Fabian, Lahti, Jari, Hüls, Anke, Hoang, Thanh T, London, Stephanie J, and Wiemels, Joseph L

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Genetics, Biological Sciences, Human Genome, Contraception/Reproduction, Pediatric, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Child, Female, Humans, Infant, Newborn, Pregnancy, Birth Order, DNA Methylation, Epigenesis, Genetic, Epigenomics, Biological sciences, Biomedical and clinical sciences
Abstract

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P

Published
2024

3. A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation

Author

Monasso, Giulietta S, Hoang, Thanh T, Mancano, Giulia, Fernández-Barrés, Sílvia, Dou, John, Jaddoe, Vincent WV, Page, Christian M, Johnson, Laura, Bustamante, Mariona, Bakulski, Kelly M, Håberg, Siri E, Ueland, Per M, Battram, Thomas, Merid, Simon K, Melén, Erik, Caramaschi, Doretta, Küpers, Leanne K, Sunyer, Jordi, Nystad, Wenche, Heil, Sandra G, Schmidt, Rebecca J, Vrijheid, Martine, Sharp, Gemma C, London, Stephanie J, and Felix, Janine F

Subjects
Biological Sciences, Genetics, Pediatric, Prevention, Nutrition, Perinatal Period - Conditions Originating in Perinatal Period, Reproductive health and childbirth, Good Health and Well Being, Infant, Newborn, Pregnancy, Child, Female, Humans, DNA Methylation, Epigenome, Birth Weight, Vitamin B 12, Epigenesis, Genetic, Fetal Blood, Vitamin B12, DNA methylation, epidemiology, cohort study, meta-analysis, PACE consortium, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Developmental Biology, Biochemistry and cell biology
Abstract

Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or cord blood (n = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value

Published
2023

6. Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation

Author

Kotsakis Ruehlmann, Anna, Sammallahti, Sara, Cortés Hidalgo, Andrea P., Bakulski, Kelly M., Binder, Elisabeth B., Campbell, Megan Loraine, Caramaschi, Doretta, Cecil, Charlotte A. M., Colicino, Elena, Cruceanu, Cristiana, Czamara, Darina, Dieckmann, Linda, Dou, John, Felix, Janine F., Frank, Josef, Håberg, Siri E., Herberth, Gunda, Hoang, Thanh T., Houtepen, Lotte C., Hüls, Anke, Koen, Nastassja, London, Stephanie J., Magnus, Maria C., Mancano, Giulia, Mulder, Rosa H., Page, Christian M., Räikkönen, Katri, Röder, Stefan, Schmidt, Rebecca J., Send, Tabea S., Sharp, Gemma, Stein, Dan J., Streit, Fabian, Tuhkanen, Johanna, Witt, Stephanie H., Zar, Heather J., Zenclussen, Ana C., Zhang, Yining, Zillich, Lea, Wright, Rosalind, Lahti, Jari, and Brunst, Kelly J.

Published
2023
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7. Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude

Author

Kadalayil, Latha, Alam, Md. Zahangir, White, Cory Haley, Ghantous, Akram, Walton, Esther, Gruzieva, Olena, Merid, Simon Kebede, Kumar, Ashish, Roy, Ritu P., Solomon, Olivia, Huen, Karen, Eskenazi, Brenda, Rzehak, Peter, Grote, Veit, Langhendries, Jean-Paul, Verduci, Elvira, Ferre, Natalia, Gruszfeld, Darek, Gao, Lu, Guan, Weihua, Zeng, Xuehuo, Schisterman, Enrique F., Dou, John F., Bakulski, Kelly M., Feinberg, Jason I., Soomro, Munawar Hussain, Pesce, Giancarlo, Baiz, Nour, Isaevska, Elena, Plusquin, Michelle, Vafeiadi, Marina, Roumeliotaki, Theano, Langie, Sabine A. S., Standaert, Arnout, Allard, Catherine, Perron, Patrice, Bouchard, Luigi, van Meel, Evelien R., Felix, Janine F., Jaddoe, Vincent W. V., Yousefi, Paul D., Ramlau-Hansen, Cecilia H., Relton, Caroline L., Tobi, Elmar W., Starling, Anne P., Yang, Ivana V., Llambrich, Maria, Santorelli, Gillian, Lepeule, Johanna, Salas, Lucas A., Bustamante, Mariona, Ewart, Susan L., Zhang, Hongmei, Karmaus, Wilfried, Röder, Stefan, Zenclussen, Ana Claudia, Jin, Jianping, Nystad, Wenche, Page, Christian M., Magnus, Maria, Jima, Dereje D., Hoyo, Cathrine, Maguire, Rachel L., Kvist, Tuomas, Czamara, Darina, Räikkönen, Katri, Gong, Tong, Ullemar, Vilhelmina, Rifas-Shiman, Sheryl L., Oken, Emily, Almqvist, Catarina, Karlsson, Robert, Lahti, Jari, Murphy, Susan K., Håberg, Siri E., London, Stephanie, Herberth, Gunda, Arshad, Hasan, Sunyer, Jordi, Grazuleviciene, Regina, Dabelea, Dana, Steegers-Theunissen, Régine P. M., Nohr, Ellen A., Sørensen, Thorkild I. A., Duijts, Liesbeth, Hivert, Marie-France, Nelen, Vera, Popovic, Maja, Kogevinas, Manolis, Nawrot, Tim S., Herceg, Zdenko, Annesi-Maesano, Isabella, Fallin, M. Daniele, Yeung, Edwina, Breton, Carrie V., Koletzko, Berthold, Holland, Nina, Wiemels, Joseph L., Melén, Erik, Sharp, Gemma C., Silver, Matt J., Rezwan, Faisal I., and Holloway, John W.

Published
2023
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11. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Heijmans, Bastiaan, ’t Hoen, Peter, van Meurs, Joyce, Jansen, Rick, Franke, Lude, Boomsma, Dorret, Pool, René, van Dongen, Jenny, Hottenga, Jouke, van Greevenbroek, Marleen, Stehouwer, Coen, van der Kallen, Carla, Schalkwijk, Casper, Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje, Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Veldink, Jan, van den Berg, Leonard, van Duijn, Cornelia, Hofman, Bert, Isaacs, Aaron, Uitterlinden, André, Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha, van ‘t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Bonder, Marc, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon, Swertz, Morris, van Zwet, Erik, Hoang, Thanh T., Lee, Yunsung, McCartney, Daniel L., Kersten, Elin T.G., Page, Christian M., Hulls, Paige M., Lee, Mikyeong, Walker, Rosie M., Breeze, Charles E., Bennett, Brian D., Burkholder, Adam B., Ward, James, Brantsæter, Anne Lise, Caspersen, Ida H., Motsinger-Reif, Alison A., Richards, Marie, White, Julie D., Zhao, Shanshan, Richmond, Rebecca C., Magnus, Maria C., Koppelman, Gerard H., Evans, Kathryn L., Marioni, Riccardo E., Håberg, Siri E., and London, Stephanie J.

Published
2024
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12. Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

Author

Solomon, Olivia, Huen, Karen, Yousefi, Paul, Küpers, Leanne K, González, Juan R, Suderman, Matthew, Reese, Sarah E, Page, Christian M, Gruzieva, Olena, Rzehak, Peter, Gao, Lu, Bakulski, Kelly M, Novoloaca, Alexei, Allard, Catherine, Pappa, Irene, Llambrich, Maria, Vives, Marta, Jima, Dereje D, Kvist, Tuomas, Baccarelli, Andrea, White, Cory, Rezwan, Faisal I, Sharp, Gemma C, Tindula, Gwen, Bergström, Anna, Grote, Veit, Dou, John F, Isaevska, Elena, Magnus, Maria C, Corpeleijn, Eva, Perron, Patrice, Jaddoe, Vincent WV, Nohr, Ellen A, Maitre, Lea, Foraster, Maria, Hoyo, Cathrine, Håberg, Siri E, Lahti, Jari, DeMeo, Dawn L, Zhang, Hongmei, Karmaus, Wilfried, Kull, Inger, Koletzko, Berthold, Feinberg, Jason I, Gagliardi, Luigi, Bouchard, Luigi, Ramlau-Hansen, Cecilia Høst, Tiemeier, Henning, Santorelli, Gillian, Maguire, Rachel L, Czamara, Darina, Litonjua, Augusto A, Langhendries, Jean-Paul, Plusquin, Michelle, Lepeule, Johanna, Binder, Elisabeth B, Verduci, Elvira, Dwyer, Terence, Carracedo, Ángel, Ferre, Natalia, Eskenazi, Brenda, Kogevinas, Manolis, Nawrot, Tim S, Munthe-Kaas, Monica C, Herceg, Zdenko, Relton, Caroline, Melén, Erik, Gruszfeld, Dariusz, Breton, Carrie, Fallin, MD, Ghantous, Akram, Nystad, Wenche, Heude, Barbara, Snieder, Harold, Hivert, Marie-France, Felix, Janine F, Sørensen, Thorkild IA, Bustamante, Mariona, Murphy, Susan K, Raikkönen, Katri, Oken, Emily, Holloway, John W, Arshad, Syed Hasan, London, Stephanie J, and Holland, Nina

Subjects
Humans, DNA Methylation, Epigenesis, Genetic, Pregnancy, Sex Characteristics, Adolescent, Child, Infant, Newborn, Female, Male, Epigenomics, Epigenome, Children, Cord blood, DNA methylation, EWAS, Sex, Digestive Diseases, Human Genome, Genetics, Prevention, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Toxicology
Abstract

BackgroundAmong children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits.MethodsWe performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268).ResultsIn newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p

Published
2022

13. Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

Author

Sharp, Gemma C, Alfano, Rossella, Ghantous, Akram, Urquiza, Jose, Rifas-Shiman, Sheryl L, Page, Christian M, Jin, Jianping, Fernández-Barrés, Silvia, Santorelli, Gillian, Tindula, Gwen, and consortium, and 36 other members of the Pregnancy and Childhood Epigenetics

Subjects
Epidemiology, Health Sciences, Genetics, Human Genome, Clinical Research, Pediatric, Contraception/Reproduction, Obesity, Reproductive health and childbirth, Body Mass Index, DNA Methylation, Epigenesis, Genetic, Epigenomics, Fathers, Female, Humans, Male, Pregnancy, Systematic Reviews as Topic, other members of the Pregnancy and Childhood Epigenetics (PACE) consortium, DNA methylation, DOHaD, Paternal, body mass index, epigenetics, fathers, pregnancy, Statistics, Public Health and Health Services, Public health
Abstract

BackgroundAccumulating evidence links paternal adiposity in the periconceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans.MethodsIn the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of coordinated epigenome-wide association studies (EWAS) of paternal prenatal body mass index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 data sets; total n = 4894) and in childhood (6 data sets; total n = 1982).ResultsWe found little evidence of an association at either time point: at all CpGs, the false-discovery-rate-adjusted P-values were >0.05. In secondary sex-stratified analyses, we found just four CpGs for which there was robust evidence of an association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes.ConclusionOur findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring-blood DNA methylation, even at imprinted regions.

Published
2021

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

Author

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

Subjects
Humans, Premature Birth, DNA, DNA Methylation, Fetal Development, Adolescent, Child, Child, Preschool, Infant, Newborn, Infant, Premature, Female, Male, Genetic Loci, Epigenome, Development, Epigenetics, Gestational age, Preterm birth, Transcriptomics, Preschool, Infant, Newborn, Premature, Genetics, Clinical Sciences
Abstract

BackgroundPreterm 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.MethodsWe 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.ResultsWe identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P

Published
2020

16. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns.

Author

Czamara, Darina, Eraslan, Gökçen, Page, Christian M, Lahti, Jari, Lahti-Pulkkinen, Marius, Hämäläinen, Esa, Kajantie, Eero, Laivuori, Hannele, Villa, Pia M, Reynolds, Rebecca M, Nystad, Wenche, Håberg, Siri E, London, Stephanie J, O'Donnell, Kieran J, Garg, Elika, Meaney, Michael J, Entringer, Sonja, Wadhwa, Pathik D, Buss, Claudia, Jones, Meaghan J, Lin, David TS, MacIsaac, Julie L, Kobor, Michael S, Koen, Nastassja, Zar, Heather J, Koenen, Karestan C, Dalvie, Shareefa, Stein, Dan J, Kondofersky, Ivan, Müller, Nikola S, Theis, Fabian J, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Räikkönen, Katri, and Binder, Elisabeth B

Subjects
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Fetal Blood, Humans, DNA, Risk Factors, Cohort Studies, DNA Methylation, Epigenesis, Genetic, Pregnancy, Genotype, Infant, Newborn, Female, Male, Gene-Environment Interaction, Genetics, Pediatric, Human Genome, Prevention, 2.1 Biological and endogenous factors, Epigenesis, Genetic, Infant, Newborn, MD Multidisciplinary
Abstract

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

Published
2019

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

Author

Küpers, Leanne K, Monnereau, Claire, Sharp, Gemma C, Yousefi, Paul, Salas, Lucas A, Ghantous, Akram, Page, Christian M, Reese, Sarah E, Wilcox, Allen J, Czamara, Darina, Starling, Anne P, Novoloaca, Alexei, Lent, Samantha, Roy, Ritu, Hoyo, Cathrine, Breton, Carrie V, Allard, Catherine, Just, Allan C, Bakulski, Kelly M, Holloway, John W, Everson, Todd M, Xu, Cheng-Jian, Huang, Rae-Chi, van der Plaat, Diana A, Wielscher, Matthias, Merid, Simon Kebede, Ullemar, Vilhelmina, Rezwan, Faisal I, Lahti, Jari, van Dongen, Jenny, Langie, Sabine AS, Richardson, Tom G, Magnus, Maria C, Nohr, Ellen A, Xu, Zongli, Duijts, Liesbeth, Zhao, Shanshan, Zhang, Weiming, Plusquin, Michelle, DeMeo, Dawn L, Solomon, Olivia, Heimovaara, Joosje H, Jima, Dereje D, Gao, Lu, Bustamante, Mariona, Perron, Patrice, Wright, Robert O, Hertz-Picciotto, Irva, Zhang, Hongmei, Karagas, Margaret R, Gehring, Ulrike, Marsit, Carmen J, Beilin, Lawrence J, Vonk, Judith M, Jarvelin, Marjo-Riitta, Bergström, Anna, Örtqvist, Anne K, Ewart, Susan, Villa, Pia M, Moore, Sophie E, Willemsen, Gonneke, Standaert, Arnout RL, Håberg, Siri E, Sørensen, Thorkild IA, Taylor, Jack A, Räikkönen, Katri, Yang, Ivana V, Kechris, Katerina, Nawrot, Tim S, Silver, Matt J, Gong, Yun Yun, Richiardi, Lorenzo, Kogevinas, Manolis, Litonjua, Augusto A, Eskenazi, Brenda, Huen, Karen, Mbarek, Hamdi, Maguire, Rachel L, Dwyer, Terence, Vrijheid, Martine, Bouchard, Luigi, Baccarelli, Andrea A, Croen, Lisa A, Karmaus, Wilfried, Anderson, Denise, de Vries, Maaike, Sebert, Sylvain, Kere, Juha, Karlsson, Robert, Arshad, Syed Hasan, Hämäläinen, Esa, Routledge, Michael N, Boomsma, Dorret I, Feinberg, Andrew P, Newschaffer, Craig J, Govarts, Eva, Moisse, Matthieu, Fallin, M Daniele, Melén, Erik, and Prentice, Andrew M

Subjects
Fetus, Humans, Prenatal Exposure Delayed Effects, Birth Weight, Folic Acid, DNA, Body Mass Index, Smoking, DNA Methylation, Epigenesis, Genetic, CpG Islands, Fetal Development, Pregnancy, Genome, Human, Adolescent, Adult, Child, Infant, Newborn, Female, Male, Genome-Wide Association Study, Epigenesis, Genetic, Genome, Human, Infant, Newborn
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

Published
2019

20. Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Author

Sammallahti, Sara, Koopman-Verhoeff, M. Elisabeth, Binter, Anne-Claire, Mulder, Rosa H., Cabré-Riera, Alba, Kvist, Tuomas, Malmberg, Anni L. K., Pesce, Giancarlo, Plancoulaine, Sabine, Heiss, Jonathan A., Rifas-Shiman, Sheryl L., Röder, Stefan W., Starling, Anne P., Wilson, Rory, Guerlich, Kathrin, Haftorn, Kristine L., Page, Christian M., Luik, Annemarie I., Tiemeier, Henning, Felix, Janine F., Raikkonen, Katri, Lahti, Jari, Relton, Caroline L., Sharp, Gemma C., Waldenberger, Melanie, Grote, Veit, Heude, Barbara, Annesi-Maesano, Isabella, Hivert, Marie-France, Zenclussen, Ana C., Herberth, Gunda, Dabelea, Dana, Grazuleviciene, Regina, Vafeiadi, Marina, Håberg, Siri E., London, Stephanie J., Guxens, Mònica, Richmond, Rebecca C., and Cecil, Charlotte A. M.

Published
2022
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24. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author

Felix, Janine F, Joubert, Bonnie R, Baccarelli, Andrea A, Sharp, Gemma C, Almqvist, Catarina, Annesi-Maesano, Isabella, Arshad, Hasan, Baïz, Nour, Bakermans-Kranenburg, Marian J, Bakulski, Kelly M, Binder, Elisabeth B, Bouchard, Luigi, Breton, Carrie V, Brunekreef, Bert, Brunst, Kelly J, Burchard, Esteban G, Bustamante, Mariona, Chatzi, Leda, Munthe-Kaas, Monica Cheng, Corpeleijn, Eva, Czamara, Darina, Dabelea, Dana, Smith, George Davey, De Boever, Patrick, Duijts, Liesbeth, Dwyer, Terence, Eng, Celeste, Eskenazi, Brenda, Everson, Todd M, Falahi, Fahimeh, Fallin, M Daniele, Farchi, Sara, Fernandez, Mariana F, Gao, Lu, Gaunt, Tom R, Ghantous, Akram, Gillman, Matthew W, Gonseth, Semira, Grote, Veit, Gruzieva, Olena, Håberg, Siri E, Herceg, Zdenko, Hivert, Marie-France, Holland, Nina, Holloway, John W, Hoyo, Cathrine, Hu, Donglei, Huang, Rae-Chi, Huen, Karen, Järvelin, Marjo-Riitta, Jima, Dereje D, Just, Allan C, Karagas, Margaret R, Karlsson, Robert, Karmaus, Wilfried, Kechris, Katerina J, Kere, Juha, Kogevinas, Manolis, Koletzko, Berthold, Koppelman, Gerard H, Küpers, Leanne K, Ladd-Acosta, Christine, Lahti, Jari, Lambrechts, Nathalie, Langie, Sabine AS, Lie, Rolv T, Liu, Andrew H, Magnus, Maria C, Magnus, Per, Maguire, Rachel L, Marsit, Carmen J, McArdle, Wendy, Melén, Erik, Melton, Phillip, Murphy, Susan K, Nawrot, Tim S, Nisticò, Lorenza, Nohr, Ellen A, Nordlund, Björn, Nystad, Wenche, Oh, Sam S, Oken, Emily, Page, Christian M, Perron, Patrice, Pershagen, Göran, Pizzi, Costanza, Plusquin, Michelle, Raikkonen, Katri, Reese, Sarah E, Reischl, Eva, Richiardi, Lorenzo, Ring, Susan, Roy, Ritu P, Rzehak, Peter, Schoeters, Greet, Schwartz, David A, Sebert, Sylvain, Snieder, Harold, Sørensen, Thorkild IA, and Starling, Anne P

Subjects
Epidemiology, Public Health, Health Sciences, Statistics, Mathematical Sciences, Child Health, Cohort Studies, DNA Methylation, Environmental Pollution, Epigenesis, Genetic, Female, Folic Acid, Humans, Infant, Newborn, Maternal Exposure, Maternal Health, Pregnancy, Prenatal Exposure Delayed Effects, Public Health and Health Services, Public health
Published
2018

25. Epigenetic timing effects on child developmental outcomes: A longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium

Author

Neumann, Alexander, primary, Sammallahti, Sara, additional, Cosin-Tomas, Marta, additional, Reese, Sarah E, additional, Suderman, Matthew, additional, Alemany, Silvia, additional, Almqvist, Catarina, additional, Andrusaityte, Sandra, additional, Arshad, Syed H, additional, Bakermans-Kranenburg, Marian J, additional, Beilin, Lawrence, additional, Breton, Carrie, additional, Bustamante, Mariona, additional, Czamara, Darina, additional, Dabelea, Dana, additional, Eng, Celeste, additional, Eskenazi, Brenda, additional, Fuemmeler, Bernard F, additional, Gilliland, Frank D, additional, Grazuleviciene, Regina, additional, Håberg, Siri E, additional, Herberth, Gunda, additional, Holland, Nina, additional, Hough, Amy, additional, Hu, Donglei, additional, Huen, Karen, additional, Hüls, Anke, additional, Jin, Jianping, additional, Julvez, Jordi, additional, Koletzko, Berthold V, additional, Koppelman, Gerard H, additional, Kull, Inger, additional, Lu, Xueling, additional, Maitre, Léa, additional, Mason, Dan, additional, Mélen, Erik, additional, Merid, Simon K, additional, Molloy, Peter L, additional, Mori, Trevor A, additional, Mulder, Rosa H, additional, Page, Christian M, additional, Richmond, Rebecca C, additional, Roder, Stefan, additional, Ross, Jason P, additional, Schellhas, Laura, additional, Sebert, Sylvain, additional, Sheppard, Dean, additional, Snieder, Harold, additional, Starling, Anne P, additional, Stein, Dan J, additional, Tindula, Gwen, additional, van IJzendoorn, Marinus H, additional, Vonk, Judith, additional, Walton, Esther, additional, Witonsky, Jonathan, additional, Xu, Cheng-Jian, additional, Yang, Ivana V, additional, Yousefi, Paul D, additional, Zar, Heather J, additional, Zenclussen, Ana C, additional, Zhang, Hongmei, additional, Tiemeier, Henning, additional, London, Stephanie J, additional, Felix, Janine F, additional, and Cecil, Charlotte, additional

Published
2024
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26. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Hoang, Thanh T., primary, Lee, Yunsung, additional, McCartney, Daniel L., additional, Kersten, Elin T.G., additional, Page, Christian M., additional, Hulls, Paige M., additional, Lee, Mikyeong, additional, Walker, Rosie M., additional, Breeze, Charles E., additional, Bennett, Brian D., additional, Burkholder, Adam B., additional, Ward, James, additional, Brantsæter, Anne Lise, additional, Caspersen, Ida H., additional, Motsinger-Reif, Alison A., additional, Richards, Marie, additional, White, Julie D., additional, Zhao, Shanshan, additional, Richmond, Rebecca C., additional, Magnus, Maria C., additional, Koppelman, Gerard H., additional, Evans, Kathryn L., additional, Marioni, Riccardo E., additional, Håberg, Siri E., additional, London, Stephanie J., additional, Heijmans, Bastiaan, additional, ’t Hoen, Peter, additional, van Meurs, Joyce, additional, Jansen, Rick, additional, Franke, Lude, additional, Boomsma, Dorret, additional, Pool, René, additional, van Dongen, Jenny, additional, Hottenga, Jouke, additional, van Greevenbroek, Marleen, additional, Stehouwer, Coen, additional, van der Kallen, Carla, additional, Schalkwijk, Casper, additional, Wijmenga, Cisca, additional, Zhernakova, Sasha, additional, Tigchelaar, Ettje, additional, Slagboom, P. Eline, additional, Beekman, Marian, additional, Deelen, Joris, additional, Van Heemst, Diana, additional, Veldink, Jan, additional, van den Berg, Leonard, additional, van Duijn, Cornelia, additional, Hofman, Bert, additional, Isaacs, Aaron, additional, Uitterlinden, André, additional, Jhamai, P. Mila, additional, Verbiest, Michael, additional, Suchiman, H. Eka, additional, Verkerk, Marijn, additional, van der Breggen, Ruud, additional, van Rooij, Jeroen, additional, Lakenberg, Nico, additional, Mei, Hailiang, additional, van Iterson, Maarten, additional, van Galen, Michiel, additional, Bot, Jan, additional, Zhernakova, Dasha, additional, van ‘t Hof, Peter, additional, Deelen, Patrick, additional, Nooren, Irene, additional, Moed, Matthijs, additional, Vermaat, Martijn, additional, Luijk, René, additional, Bonder, Marc, additional, van Dijk, Freerk, additional, Arindrarto, Wibowo, additional, Kielbasa, Szymon, additional, Swertz, Morris, additional, and van Zwet, Erik, additional

Published
2024
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27. Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines

Author

Mygland, Line, Brinch, Shoshy Alam, Strand, Martin Frank, Olsen, Petter Angell, Aizenshtadt, Aleksandra, Lund, Kaja, Solberg, Nina Therese, Lycke, Max, Thorvaldsen, Tor Espen, Espada, Sandra, Misaghian, Dorna, Page, Christian M., Agafonov, Oleg, Nygård, Ståle, Chi, Nai-Wen, Lin, Eva, Tan, Jenille, Yu, Yihong, Costa, Mike, Krauss, Stefan, and Waaler, Jo

Published
2021
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28. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium

Author

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

Subjects
Biological Sciences, Genetics, Perinatal Period - Conditions Originating in Perinatal Period, Contraception/Reproduction, Pediatric, Human Genome, Obesity, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Adult, Body Mass Index, Cohort Studies, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Humans, Infant, Newborn, Male, Maternal Inheritance, Mothers, Pregnancy, Pregnancy Outcome, Prenatal Exposure Delayed Effects, Medical and Health Sciences, Genetics & Heredity
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 (

Published
2017

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

Author

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

Published
2021
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30. Impaired glucose tolerance and cardiovascular risk factors in relation to infertility: a Mendelian randomization analysis in the Norwegian Mother, Father, and Child Cohort Study

Author

Hernáez, Álvaro, primary, Lee, Yunsung, additional, Page, Christian M, additional, Skåra, Karoline H, additional, Håberg, Siri E, additional, Magnus, Per, additional, Njølstad, Pål R, additional, Andreassen, Ole A, additional, Corfield, Elizabeth C, additional, Havdahl, Alexandra, additional, Fraser, Abigail, additional, Burgess, Stephen, additional, Lawlor, Deborah A, additional, and Magnus, Maria C, additional

Published
2023
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31. Maternal caffeine consumption during pregnancy and offspring cord blood DNA methylation: an epigenome-wide association study meta-analysis

Author

Schellhas, Laura, primary, Monasso, Giulietta S, additional, Felix, Janine F, additional, Jaddoe, Vincent WV, additional, Huang, Peiyuan, additional, Fernández-Barrés, Sílvia, additional, Vrijheid, Martine, additional, Pesce, Giancarlo, additional, Annesi-Maesano, Isabella, additional, Page, Christian M, additional, Brantsæter, Anne-Lise, additional, Bekkhus, Mona, additional, Håberg, Siri E, additional, London, Stephanie J, additional, Munafò, Marcus R, additional, Zuccolo, Luisa, additional, and Sharp, Gemma C, additional

Published
2023
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33. Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Author

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

Published
2019
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34. Impaired glucose tolerance and cardiovascular risk factors in relation to infertility: a Mendelian randomization analysis in the Norwegian Mother, Father, and Child Cohort Study.

Author

Hernáez, Álvaro, Lee, Yunsung, Page, Christian M, Skåra, Karoline H, Håberg, Siri E, Magnus, Per, Njølstad, Pål R, Andreassen, Ole A, Corfield, Elizabeth C, Havdahl, Alexandra, Fraser, Abigail, Burgess, Stephen, Lawlor, Deborah A, and Magnus, Maria C

Subjects
INFERTILITY, FERTILITY clinics, CARDIOVASCULAR diseases risk factors, DIASTOLIC blood pressure, MULTIPLE comparisons (Statistics), HDL cholesterol, LDL cholesterol
Abstract

STUDY QUESTION Are impaired glucose tolerance (as measured by fasting glucose, glycated hemoglobin, and fasting insulin) and cardiovascular disease risk (as measured by low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure) causally related to infertility? SUMMARY ANSWER Genetic instruments suggest that higher fasting insulin may increase infertility in women. WHAT IS KNOWN ALREADY Observational evidence suggests a shared etiology between impaired glucose tolerance, cardiovascular risk, and fertility problems. STUDY DESIGN, SIZE, DURATION This study included two-sample Mendelian randomization (MR) analyses, in which we used genome-wide association summary data that were publicly available for the biomarkers of impaired glucose tolerance and cardiovascular disease, and sex-specific genome-wide association studies (GWASs) of infertility conducted in the Norwegian Mother, Father, and Child Cohort Study. PARTICIPANTS/MATERIALS, SETTING, METHODS There were 68 882 women (average age 30, involved in 81 682 pregnancies) and 47 474 of their male partners (average age 33, 55 744 pregnancies) who had available genotype data and who provided self-reported information on time-to-pregnancy and use of ARTs. Of couples, 12% were infertile (having tried to conceive for ≥12 months or used ARTs to conceive). We applied the inverse variance weighted method with random effects to pool data across variants and a series of sensitivity analyses to explore genetic instrument validity. (We checked the robustness of genetic instruments and the lack of unbalanced horizontal pleiotropy, and we used methods that are robust to population stratification.) Findings were corrected for multiple comparisons by the Bonferroni method (eight exposures: P -value < 0.00625). MAIN RESULTS AND THE ROLE OF CHANCE In women, increases in genetically determined fasting insulin levels were associated with greater odds of infertility (+1 log(pmol/l): odds ratio 1.60, 95% CI 1.17 to 2.18, P -value = 0.003). The results were robust in the sensitivity analyses exploring the validity of MR assumptions and the role of pleiotropy of other cardiometabolic risk factors. There was also evidence of higher glucose and glycated hemoglobin causing infertility in women, but the findings were imprecise and did not pass our P -value threshold for multiple testing. The results for lipids and blood pressure were close to the null, suggesting that these did not cause infertility. LIMITATIONS, REASONS FOR CAUTION We did not know if underlying causes of infertility were in the woman, man, or both. Our analyses only involved couples who had conceived. We did not have data on circulating levels of cardiometabolic risk factors, and we opted to conduct an MR analysis using GWAS summary statistics. No sex-specific genetic instruments on cardiometabolic risk factors were available. Our results may be affected by selection and misclassification bias. Finally, the characteristics of our study sample limit the generalizability of our results to populations of non-European ancestry. WIDER IMPLICATIONS OF THE FINDINGS Treatments for lower fasting insulin levels may reduce the risk of infertility in women. STUDY FUNDING/COMPETING INTEREST(S) The MoBa Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Norwegian Ministry of Education and Research. This work was supported by the European Research Council [grant numbers 947684, 101071773, 293574, 101021566], the Research Council of Norway [grant numbers 262700, 320656, 274611], the South-Eastern Norway Regional Health Authority [grant numbers 2020022, 2021045], and the British Heart Foundation [grant numbers CH/F/20/90003, AA/18/1/34219]. Open Access funding was provided by the Norwegian Institute of Public Health. The funders had no role in the study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the article for publication. D.A.L. has received research support from National and International government and charitable bodies, Roche Diagnostics and Medtronic for research unrelated to the current work. O.A.A. has been a consultant to HealthLytix. The rest of the authors declare that no competing interests exist. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Parental genetically predicted liability for coronary heart disease and risk of adverse pregnancy outcomes: a cohort study

Author

Hernaez, Alvaro, primary, Skara, Karoline H., additional, Page, Christian M., additional, Mitter, Vera R., additional, Hernandez, Marta H., additional, Magnus, Per, additional, Njolstad, Pal Rasmus, additional, Andreassen, Ole A., additional, Corfield, Elizabeth C., additional, Havdahl, Alexandra, additional, Naess, Oyvind E., additional, Brumpton, Ben M, additional, Asvold, Bjorn Olav, additional, Lawlor, Deborah A., additional, Fraser, Abigail, additional, and Magnus, Maria C., additional

Published
2023
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37. Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array

Author

Lee, Yunsung, Haftorn, Kristine L., Denault, William R. P., Nustad, Haakon E., Page, Christian M., Lyle, Robert, Lee-Ødegård, Sindre, Moen, Gunn-Helen, Prasad, Rashmi B., Groop, Leif C., Sletner, Line, Sommer, Christine, Magnus, Maria C., Gjessing, Håkon K., Harris, Jennifer R., Magnus, Per, Håberg, Siri E., Jugessur, Astanand, and Bohlin, Jon

Published
2020
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40. Maternal caffeine consumption during pregnancy and offspring cord blood DNA methylation: a meta-analysis of epigenome-wide association studies

Author

Schellhas, Laura, primary, Monasso, Giulietta S, additional, Felix, Janine F, additional, Jaddoe, Vincent WV, additional, Huang, Peiyuan, additional, Fernández-Barrés, Sílvia, additional, Vrijheid, Martine, additional, Pesce, Giancarlo, additional, Annesi-Maesano, Isabella, additional, Page, Christian M, additional, Brantsæter, Anne-Lise, additional, Bekkhus, Mona, additional, Håberg, Siri E, additional, London, Stephanie J, additional, Munafò, Marcus R, additional, Zuccolo, Luisa, additional, and Sharp, Gemma C, additional

Published
2023
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41. Maternal caffeine consumption during pregnancy and offspring cord blood DNA methylation:an epigenome-wide association study meta-analysis

Author

Schellhas, Laura, Monasso, Giulietta S., Felix, Janine F., Jaddoe, Vincent Wv, Huang, Peiyuan, Fernández-Barrés, Sílvia, Vrijheid, Martine, Pesce, Giancarlo, Annesi-Maesano, Isabella, Page, Christian M., Brantsæter, Anne Lise, Bekkhus, Mona, Håberg, Siri E., London, Stephanie J., Munafò, Marcus R., Zuccolo, Luisa, Sharp, Gemma C., Schellhas, Laura, Monasso, Giulietta S., Felix, Janine F., Jaddoe, Vincent Wv, Huang, Peiyuan, Fernández-Barrés, Sílvia, Vrijheid, Martine, Pesce, Giancarlo, Annesi-Maesano, Isabella, Page, Christian M., Brantsæter, Anne Lise, Bekkhus, Mona, Håberg, Siri E., London, Stephanie J., Munafò, Marcus R., Zuccolo, Luisa, and Sharp, Gemma C.

Abstract

Background: Prenatal caffeine exposure may influence offspring health via DNA methylation, but no large studies have tested this. Materials & methods: Epigenome-wide association studies and differentially methylated regions in cord blood (450k or EPIC Illumina arrays) were meta-analyzed across six European cohorts (n = 3725). Differential methylation related to self-reported caffeine intake (mg/day) from coffee, tea and cola was compared with assess whether caffeine is driving effects. Results: One CpG site (cg19370043, PRRX1) was associated with caffeine and another (cg14591243, STAG1) with cola intake. A total of 12-22 differentially methylated regions were detected with limited overlap across caffeinated beverages. Conclusion: We found little evidence to support an intrauterine effect of caffeine on offspring DNA methylation. Statistical power limitations may have impacted our findings.

Published
2023

42. A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation

Author

Monasso, Giulietta S., Hoang, Thanh T., Mancano, Giulia, Fernández-Barrés, Sílvia, Dou, John, Jaddoe, Vincent W.V., Page, Christian M., Johnson, Laura, Bustamante, Mariona, Bakulski, Kelly M., Håberg, Siri E., Ueland, Per M., Battram, Thomas, Merid, Simon K., Melén, Erik, Caramaschi, Doretta, Küpers, Leanne K., Sunyer, Jordi, Nystad, Wenche, Heil, Sandra G., Schmidt, Rebecca J., Vrijheid, Martine, Sharp, Gemma C., London, Stephanie J., Felix, Janine F., Monasso, Giulietta S., Hoang, Thanh T., Mancano, Giulia, Fernández-Barrés, Sílvia, Dou, John, Jaddoe, Vincent W.V., Page, Christian M., Johnson, Laura, Bustamante, Mariona, Bakulski, Kelly M., Håberg, Siri E., Ueland, Per M., Battram, Thomas, Merid, Simon K., Melén, Erik, Caramaschi, Doretta, Küpers, Leanne K., Sunyer, Jordi, Nystad, Wenche, Heil, Sandra G., Schmidt, Rebecca J., Vrijheid, Martine, Sharp, Gemma C., London, Stephanie J., and Felix, Janine F.

Abstract

Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or cord blood (n = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4–10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood (P FDR<0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.

Published
2023

43. Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation

Author

Kotsakis Ruehlmann, Anna, Sammallahti, Sara, Cortés Hidalgo, Andrea P., Bakulski, Kelly M., Binder, Elisabeth B., Campbell, Megan Loraine, Caramaschi, Doretta, Cecil, Charlotte A. M., Colicino, Elena, Cruceanu, Cristiana, Czamara, Darina, Dieckmann, Linda, Dou, John, Felix, Janine F., Frank, Josef, Håberg, Siri E., Herberth, Gunda, Hoang, Thanh T., Houtepen, Lotte C., Hüls, Anke, Koen, Nastassja, London, Stephanie J., Magnus, Maria C., Mancano, Giulia, Mulder, Rosa H., Page, Christian M., Räikkönen, Katri, Röder, Stefan, Schmidt, Rebecca J., Send, Tabea S., Sharp, Gemma, Stein, Dan J., Streit, Fabian, Tuhkanen, Johanna, Witt, Stephanie H., Zar, Heather J., Zenclussen, Ana C., Zhang, Yining, Zillich, Lea, Wright, Rosalind, Lahti, Jari, and Brunst, Kelly J.

Abstract

Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N= 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.

Published
2024
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44. Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns: Findings From the Pregnancy and Childhood Epigenetics Consortium

Author

Kazmi, Nabila, Sharp, Gemma C., Reese, Sarah E., Vehmeijer, Florianne O., Lahti, Jari, Page, Christian M., Zhang, Weiming, Rifas-Shiman, Sheryl L., Rezwan, Faisal I., Simpkin, Andrew J., Burrows, Kimberley, Richardson, Tom G., Santos Ferreira, Diana L., Fraser, Abigail, Harmon, Quaker E., Zhao, Shanshan, Jaddoe, Vincent W.V., Czamara, Darina, Binder, Elisabeth B., Magnus, Maria C., Håberg, Siri E., Nystad, Wenche, Nohr, Ellen A., Starling, Anne P., Kechris, Katerina J., Yang, Ivana V., DeMeo, Dawn L., Litonjua, Augusto A., Baccarelli, Andrea, Oken, Emily, Holloway, John W., Karmaus, Wilfried, Arshad, Syed H., Dabelea, Dana, Sørensen, Thorkild I.A., Laivuori, Hannele, Raikkonen, Katri, Felix, Janine F., London, Stephanie J., Hivert, Marie-France, Gaunt, Tom R., Lawlor, Debbie A., and Relton, Caroline L.

Published
2019
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45. Epigenome-wide association study of serum folate in maternal peripheral blood leukocytes

Author

Fragoso-Bargas, Nicolas, primary, Page, Christian M, additional, Joubert, Bonnie R, additional, London, Stephanie J, additional, Lee-Ødegård, Sindre, additional, Opsahl, Julia O, additional, Sletner, Line, additional, Jenum, Anne K, additional, Qvigstad, Elisabeth, additional, Prasad, Rashmi B, additional, Moen, Gunn-Helen, additional, Birkeland, Kåre I, additional, and Sommer, Christine, additional

Published
2023
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47. Additional file 1 of Stability selection enhances feature selection and enables accurate prediction of gestational age using only five DNA methylation sites

Author

Haftorn, Kristine L., Romanowska, Julia, Lee, Yunsung, Page, Christian M., Magnus, Per M., Håberg, Siri E., Bohlin, Jon, Jugessur, Astanand, and Denault, William R. P.

Abstract

Additional file 1. Supplementary Table 1. Relationship between the number of false discoveries, selection probability threshold, and the number of CpGs considered stably predictive of GA; Supplementary Table 2. Prediction performance of epigenetic GA clocks developed from stably selected CpGs, in addition to a clock developed using a standard framework with LASSO; Supplementary Table 3. Output from a GAM regression of GA on 15 stably selected CpGs; Supplementary Table 4. Regulatory region localization of CpGs stably predictive of GA; Supplementary Table 5. Overlap between stability selection results and results from a cell-type specific analysis of the association between DNA methylation and GA.

Published
2023
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48. The X-factor in ART: does the use of Assisted Reproductive Technologies influence DNA methylation on the X chromosome?

Author

Romanowska, Julia, primary, Nustad, Haakon E., additional, Page, Christian M., additional, Denault, William R.P., additional, Bohlin, Jon, additional, Lee, Yunsung, additional, Magnus, Maria C., additional, Haftorn, Kristine L., additional, Gjerdevik, Miriam, additional, Novakovic, Boris, additional, Saffery, Richard, additional, Gjessing, Håkon K., additional, Lyle, Robert, additional, Magnus, Per, additional, Håberg, Siri E., additional, and Jugessur, Astanand, additional

Published
2022
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