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1. 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

2. 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

3. 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, Pediatric, Human Genome, Perinatal Period - Conditions Originating in Perinatal Period, Pregnancy, Prevention, Women's Health, Obesity, Nutrition, Maternal Health, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Adult, Body Mass Index, Cohort Studies, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Humans, Infant, Newborn, Male, Maternal Inheritance, Mothers, 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

6. 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 A. S., 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 R. L., Håberg, Siri E., Sørensen, Thorkild I. A., 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, Prentice, Andrew M., Kajantie, Eero, Almqvist, Catarina, Oken, Emily, Dabelea, Dana, Boezen, H. Marike, Melton, Phillip E., Wright, Rosalind J., Koppelman, Gerard H., Trevisi, Letizia, Hivert, Marie-France, Sunyer, Jordi, Munthe-Kaas, Monica C., Murphy, Susan K., Corpeleijn, Eva, Wiemels, Joseph, Holland, Nina, Herceg, Zdenko, Binder, Elisabeth B., Davey Smith, George, Jaddoe, Vincent W. V., Lie, Rolv T., Nystad, Wenche, London, Stephanie J., Lawlor, Debbie A., Relton, Caroline L., Snieder, Harold, and Felix, Janine F.

Published
2019
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7. Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence

Author

Choudhary, Priyanka, Monasso, Giulietta S., Karhunen, Ville, Ronkainen, Justiina, Mancano, Giulia, Howe, Caitlin G., Niu, Zhongzheng, Zeng, Xuehuo, Guan, Weihua, Dou, John, Feinberg, Jason I., Mordaunt, Charles, Pesce, Giancarlo, Baïz, Nour, Alfano, Rossella, Martens, Dries S., Wang, Congrong, Isaevska, Elena, Keikkala, Elina, Mustaniemi, Sanna, Thio, Chris H. L., Fraszczyk, Eliza, Tobi, Elmar W., Starling, Anne P., Cosin-Tomas, Marta, Urquiza, Jose, Röder, Stefan, Hoang, Thanh T., Page, Christian, Jima, Dereje D., House, John S., Maguire, Rachel L., Ott, Raffael, Pawlow, Xenia, Sirignano, Lea, Zillich, Lea, Malmberg, Anni, Rauschert, Sebastian, Melton, Phillip, Gong, Tong, Karlsson, Robert, Fore, Ruby, Perng, Wei, Laubach, Zachary M., Czamara, Darina, Sharp, Gemma, Breton, Carrie V., Schisterman, Enrique, Yeung, Edwina, Mumford, Sunni L., Fallin, M. Daniele, LaSalle, Janine M., Schmidt, Rebecca J., Bakulski, Kelly M., Annesi-Maesano, Isabella, Heude, Barbara, Nawrot, Tim S., Plusquin, Michelle, Ghantous, Akram, Herceg, Zdenko, Nisticò, Lorenza, Vafeiadi, Marina, Kogevinas, Manolis, Vääräsmäki, Marja, Kajantie, Eero, Snieder, Harold, Corpeleijn, Eva, Steegers-Theunissen, Regine P. M., Yang, Ivana V., Dabelea, Dana, Fossati, Serena, Zenclussen, Ana C., Herberth, Gunda, Magnus, Maria, Håberg, Siri E., London, Stephanie J., Munthe-Kaas, Monica C., Murphy, Susan K., Hoyo, Cathrine, Ziegler, Anette-G, Hummel, Sandra, Witt, Stephanie H., Streit, Fabian, Frank, Josef, Räikkönen, Katri, Lahti, Jari, Huang, Rae-chi, Almqvist, Catarina, Hivert, Marie-France, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Kantomaa, Marko, Felix, Janine F., Sebert, Sylvain, Choudhary, Priyanka, Monasso, Giulietta S., Karhunen, Ville, Ronkainen, Justiina, Mancano, Giulia, Howe, Caitlin G., Niu, Zhongzheng, Zeng, Xuehuo, Guan, Weihua, Dou, John, Feinberg, Jason I., Mordaunt, Charles, Pesce, Giancarlo, Baïz, Nour, Alfano, Rossella, Martens, Dries S., Wang, Congrong, Isaevska, Elena, Keikkala, Elina, Mustaniemi, Sanna, Thio, Chris H. L., Fraszczyk, Eliza, Tobi, Elmar W., Starling, Anne P., Cosin-Tomas, Marta, Urquiza, Jose, Röder, Stefan, Hoang, Thanh T., Page, Christian, Jima, Dereje D., House, John S., Maguire, Rachel L., Ott, Raffael, Pawlow, Xenia, Sirignano, Lea, Zillich, Lea, Malmberg, Anni, Rauschert, Sebastian, Melton, Phillip, Gong, Tong, Karlsson, Robert, Fore, Ruby, Perng, Wei, Laubach, Zachary M., Czamara, Darina, Sharp, Gemma, Breton, Carrie V., Schisterman, Enrique, Yeung, Edwina, Mumford, Sunni L., Fallin, M. Daniele, LaSalle, Janine M., Schmidt, Rebecca J., Bakulski, Kelly M., Annesi-Maesano, Isabella, Heude, Barbara, Nawrot, Tim S., Plusquin, Michelle, Ghantous, Akram, Herceg, Zdenko, Nisticò, Lorenza, Vafeiadi, Marina, Kogevinas, Manolis, Vääräsmäki, Marja, Kajantie, Eero, Snieder, Harold, Corpeleijn, Eva, Steegers-Theunissen, Regine P. M., Yang, Ivana V., Dabelea, Dana, Fossati, Serena, Zenclussen, Ana C., Herberth, Gunda, Magnus, Maria, Håberg, Siri E., London, Stephanie J., Munthe-Kaas, Monica C., Murphy, Susan K., Hoyo, Cathrine, Ziegler, Anette-G, Hummel, Sandra, Witt, Stephanie H., Streit, Fabian, Frank, Josef, Räikkönen, Katri, Lahti, Jari, Huang, Rae-chi, Almqvist, Catarina, Hivert, Marie-France, Jaddoe, Vincent W. V., Järvelin, Marjo-Riitta, Kantomaa, Marko, Felix, Janine F., and Sebert, Sylvain

Abstract

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

Published
2023

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

Author

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

Published
2022
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10. 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, Yousefi, Paul, Kupers, Leanne, Ruiz-Arenas, Carlos, Jaddoe, Vincent WV, Demeo, Dawn, Fossati, Serena, Wright, John, Huen, Karen, Popovic, Maja, Nohr, Ellen A, Davey Smith, George, Lepeule, Johanna, Baccarelli, Andrea, Magnus, Maria C, Nystad, Wenche, Casas, Maribel, Oken, Emily, Håberg, Siri E, Vafeiadi, Marina, Roumeliotaki, Theano, Vrijheid, Martine, Munthe-Kaas, Monica C, Eskenazi, Brenda, Ronfani, Luca, Holland, Nina, Chatzi, Leda, Meltzer, Helle Margrete, Herceg, Zdenko, Plusquin, Michelle, Bustamante, Mariona, Hivert, Marie-France, Lawlor, Deborah A, Sørensen, Thorkild IA, London, Stephanie J, Felix, Janine F, Relton Caroline, L, Sharp, Gemma C, ALFANO, Rossella, Ghantous, Akram, Urquiza, Jose, Rifas-Shiman, Sheryl L, Page, Christian M, Jin, Jianping, Fernández-Barrés, Silvia, Santorelli, Gillian, and Tindula, Gwen

Subjects
0301 basic medicine, Male, Epigenomics, Candidate gene, Offspring, Epidemiology, Physiology, fathers, body mass index, Reproductive health and childbirth, Biology, DNA methylation, DOHaD, Paternal, epigenetics, pregnancy, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, Genetic, Clinical Research, medicine, Genetics, Humans, AcademicSubjects/MED00860, 030212 general & internal medicine, Epigenetics, Obesity, Genetic association, Pediatric, Pregnancy, Contraception/Reproduction, Human Genome, Statistics, General Medicine, medicine.disease, 030104 developmental biology, Public Health and Health Services, other members of the Pregnancy and Childhood Epigenetics (PACE) consortium, Female, paternal, Genomic imprinting, Body mass index, Epigenesis, Systematic Reviews as Topic
Abstract

Background Accumulating 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. Methods In 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). Results We 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. Conclusion Our 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
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11. The Norwegian childhood cancer biobank

Author

Hermansen, Johanne U., primary, Wojcik, Dorota M., additional, Robinson, Nina, additional, Pahnke, Jens, additional, Haugland, Hans Kristian, additional, Jamtøy, Ann Helen, additional, Flægstad, Trond, additional, Halvorsen, Hanne, additional, Lund, Bendik, additional, Baumbusch, Lars O., additional, and Munthe‐Kaas, Monica C., additional

Published
2021
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12. Management of Hyperleukocytosis in Pediatric Acute Myeloid Leukemia Using Immediate Chemotherapy without Leukapheresis, in Protocol NOPHO-DBH AML-2012

Author

Zeller, Bernward, Arad-Cohen, Nira, Cheuk, Daniel, De Moerloose, Barbara, Fernandez Navarro, Jose Maria, Hasle, Henrik, Kirsi, Jahnukainen, Juul-Dam, Kristian, Kaspers, Gertjan J.L., Kovalova, Zhanna, Lausen, Birgitte, Munthe-Kaas, Monica C., Norén-Nyström, Ulrika, Palle, Josefine, Pasauliene, Ramune, Pronk, Cornelis Jan, Saks, Kadri, Tierens, Anne Maria, and Abrahamsson, Jonas

Published
2023
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13. Chip-AML22 Master Protocol: An Open-Label Clinical Trial in Newly Diagnosed Pediatric De Novo Acute Myeloid Leukemia (AML) Patients Including a Linked Phase II Trial with Quizartinib in FLT3-ITD/ NPM1wt Patients - a Study By the NOPHO-DB-SHIP Consortium

Author

Kaspers, Gertjan J.L., Wijnen, Noa E., Koedijk, Joost B., Ishimaru, Sae, Benedictus, Renske, Van Opstal, Ellen C., Van Tinteren, Harm, Zwaan, C. Michel, Biserna, Noha, Downs, Pamela, Duong, Yvonne, Kamel, Yasser Mostafa, Abrahamsson, Jonas, Arad-Cohen, Nira, Bodmer, Nicole, Castillo, Luis, Cheuk, Daniel, Costa, Vitor, De Moerloose, Barbara, Fernandez Navarro, Jose Maria, Fogelstrand, Linda, Goemans, Bianca F., Hasle, Henrik, Jonsson, Olafur G., Kovalova, Zhanna, Munthe-Kaas, Monica C., Norén-Nyström, Ulrika, Palmu, Sauli, Pasauliene, Ramune, Saks, Kadri, Tierens, Anne Maria, Turkiewicz, Dominik, and Pronk, Cornelis Jan

Published
2023
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14. 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 I A, 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, Melén, Erik, 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 I A, 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

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
2021

18. The Norwegian childhood cancer biobank.

Author

Hermansen, Johanne U., Wojcik, Dorota M., Robinson, Nina, Pahnke, Jens, Haugland, Hans Kristian, Jamtøy, Ann Helen, Flægstad, Trond, Halvorsen, Hanne, Lund, Bendik, Baumbusch, Lars O., and Munthe‐Kaas, Monica C.

Published
2022
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20. Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

Author

Sharp, Gemma C, primary, Alfano, Rossella, additional, Ghantous, Akram, additional, Urquiza, Jose, additional, Rifas-Shiman, Sheryl L, additional, Page, Christian M, additional, Jin, Jianping, additional, Fernández-Barrés, Silvia, additional, Santorelli, Gillian, additional, Tindula, Gwen, additional, Yousefi, Paul, additional, Kupers, Leanne, additional, Ruiz-Arenas, Carlos, additional, Jaddoe, Vincent WV, additional, DeMeo, Dawn, additional, Fossati, Serena, additional, Wright, John, additional, Huen, Karen, additional, Popovic, Maja, additional, Nohr, Ellen A, additional, Smith, George Davey, additional, Lepeule, Johanna, additional, Baccarelli, Andrea, additional, Magnus, Maria C, additional, Nystad, Wenche, additional, Casas, Maribel, additional, Oken, Emily, additional, Håberg, Siri E, additional, Vafeiadi, Marina, additional, Roumeliotaki, Theano, additional, Vrijheid, Martine, additional, Munthe-Kaas, Monica C, additional, Eskenazi, Brenda, additional, Ronfani, Luca, additional, Holland, Nina, additional, Chatzi, Leda, additional, Meltzer, Helle Margrete, additional, Herceg, Zdenko, additional, Plusquin, Michelle, additional, Bustamante, Mariona, additional, Hivert, Marie-France, additional, Lawlor, Deborah A, additional, Sørensen, Thorkild IA, additional, London, Stephanie J, additional, Felix, Janine F, additional, and Relton, Caroline L, additional

Published
2020
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22. 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, primary, Salas, Lucas A, additional, Monnereau, Claire, additional, Allard, Catherine, additional, Yousefi, Paul, additional, Everson, Todd M, additional, Bohlin, Jon, additional, Xu, Zongli, additional, Huang, Rae-Chi, additional, Reese, Sarah E, additional, Xu, Cheng-Jian, additional, Baïz, Nour, additional, Hoyo, Cathrine, additional, Agha, Golareh, additional, Roy, Ritu, additional, Holloway, John W, additional, Ghantous, Akram, additional, Merid, Simon Kebede, additional, Bakulski, Kelly M, additional, Küpers, Leanne K, additional, Zhang, Hongmei, additional, Richmond, Rebecca C, additional, Page, Christian M, additional, Duijts, Liesbeth, additional, Lie, Rolv T, additional, Melton, Phillip E, additional, Vonk, Judith M, additional, Nohr, Ellen A, additional, Williams-DeVane, CharLynda, additional, Huen, Karen, additional, Rifas-Shiman, Sheryl L, additional, Ruiz-Arenas, Carlos, additional, Gonseth, Semira, additional, Rezwan, Faisal I, additional, Herceg, Zdenko, additional, Ekström, Sandra, additional, Croen, Lisa, additional, Falahi, Fahimeh, additional, Perron, Patrice, additional, Karagas, Margaret R, additional, Quraishi, Bilal Mohammed, additional, Suderman, Matthew, additional, Magnus, Maria C, additional, Jaddoe, Vincent WV, additional, Taylor, Jack A, additional, Anderson, Denise, additional, Zhao, Shanshan, additional, Smit, Henriette A, additional, Josey, Michele J, additional, Bradman, Asa, additional, Baccarelli, Andrea A, additional, Bustamante, Mariona, additional, Håberg, Siri E, additional, Pershagen, Göran, additional, Hertz-Picciotto, Irva, additional, Newschaffer, Craig, additional, Corpeleijn, Eva, additional, Bouchard, Luigi, additional, Lawlor, Debbie A, additional, Maguire, Rachel L, additional, Barcellos, Lisa F, additional, Smith, George Davey, additional, Eskenazi, Brenda, additional, Karmaus, Wilfried, additional, Marsit, Carmen J, additional, Hivert, Marie-France, additional, Snieder, Harold, additional, Fallin, M Daniele, additional, Melén, Erik, additional, Munthe-Kaas, Monica C, additional, Arshad, Hasan, additional, Wiemels, Joseph L, additional, Annesi-Maesano, Isabella, additional, Vrijheid, Martine, additional, Oken, Emily, additional, Holland, Nina, additional, Murphy, Susan K, additional, Sørensen, Thorkild IA, additional, Koppelman, Gerard H, additional, Newnham, John P, additional, Wilcox, Allen J, additional, Nystad, Wenche, additional, London, Stephanie J, additional, Felix, Janine F, additional, and Relton, Caroline L, additional

Published
2017
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23. 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, Clar Lynda, 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 J., Magnus, Maria C., Jaddoe, Vincent W V, Taylor, Jack A, Anderson, Denise, Zhao, Shanshan, Smit, Henriette A., Josey, Michele J., Bradman, Asa, Baccarelli, Andrea A., Bustamante, Mariona, Håberg, Siri E., Pershagen, Göran, Hertz-Picciotto, Irva, Newschaffer, Craig, Corpeleijn, Eva, Bouchard, Luigi, Lawlor, Debbie A., Maguire, Rachel L., Barcellos, Lisa F., 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, S Hasan, Wiemels, Joseph L., Annesi-Maesano, Isabella, Vrijheid, Martine, Oken, Emily, Holland, Nina, Murphy, Susan K., Sørensen, Thorkild I A, Koppelman, Gerard H, Newnham, John P, Wilcox, Allen J., Nystad, Wenche, London, Stephanie J., Felix, Janine F., Relton, Caroline L, 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, Clar Lynda, 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 J., Magnus, Maria C., Jaddoe, Vincent W V, Taylor, Jack A, Anderson, Denise, Zhao, Shanshan, Smit, Henriette A., Josey, Michele J., Bradman, Asa, Baccarelli, Andrea A., Bustamante, Mariona, Håberg, Siri E., Pershagen, Göran, Hertz-Picciotto, Irva, Newschaffer, Craig, Corpeleijn, Eva, Bouchard, Luigi, Lawlor, Debbie A., Maguire, Rachel L., Barcellos, Lisa F., 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, S Hasan, Wiemels, Joseph L., Annesi-Maesano, Isabella, Vrijheid, Martine, Oken, Emily, Holland, Nina, Murphy, Susan K., Sørensen, Thorkild I A, Koppelman, Gerard H, Newnham, John P, Wilcox, Allen J., Nystad, Wenche, London, Stephanie J., Felix, Janine F., and Relton, Caroline L

Published
2017

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

Abstract

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.

Published
2017

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

Author

UMC Utrecht, Public Health Epidemiologie, Circulatory Health, Child Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, 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, Clar Lynda, 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 J., Magnus, Maria C., Jaddoe, Vincent W V, Taylor, Jack A, Anderson, Denise, Zhao, Shanshan, Smit, Henriette A., Josey, Michele J., Bradman, Asa, Baccarelli, Andrea A., Bustamante, Mariona, Håberg, Siri E., Pershagen, Göran, Hertz-Picciotto, Irva, Newschaffer, Craig, Corpeleijn, Eva, Bouchard, Luigi, Lawlor, Debbie A., Maguire, Rachel L., Barcellos, Lisa F., 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, S Hasan, Wiemels, Joseph L., Annesi-Maesano, Isabella, Vrijheid, Martine, Oken, Emily, Holland, Nina, Murphy, Susan K., Sørensen, Thorkild I A, Koppelman, Gerard H, Newnham, John P, Wilcox, Allen J., Nystad, Wenche, London, Stephanie J., Felix, Janine F., Relton, Caroline L, UMC Utrecht, Public Health Epidemiologie, Circulatory Health, Child Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, 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, Clar Lynda, 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 J., Magnus, Maria C., Jaddoe, Vincent W V, Taylor, Jack A, Anderson, Denise, Zhao, Shanshan, Smit, Henriette A., Josey, Michele J., Bradman, Asa, Baccarelli, Andrea A., Bustamante, Mariona, Håberg, Siri E., Pershagen, Göran, Hertz-Picciotto, Irva, Newschaffer, Craig, Corpeleijn, Eva, Bouchard, Luigi, Lawlor, Debbie A., Maguire, Rachel L., Barcellos, Lisa F., 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, S Hasan, Wiemels, Joseph L., Annesi-Maesano, Isabella, Vrijheid, Martine, Oken, Emily, Holland, Nina, Murphy, Susan K., Sørensen, Thorkild I A, Koppelman, Gerard H, Newnham, John P, Wilcox, Allen J., Nystad, Wenche, London, Stephanie J., Felix, Janine F., and Relton, Caroline L

Published
2017

26. Genetics and epigenetics of childhood asthma

Author

Munthe-Kaas, Monica C., Willemse, Brigitte W.M., Koppelman, Gerard H., and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Candidate gene association studies, DNA methylation, Positional cloning, Histone modification, Genome-wide associations studies, Micrornas
Abstract

Asthma is a complex disorder caused by interaction of genetic and environmental factors. In the last decade a lot of genes related to asthma and atopy were discovered. Candidate gene studies showed the involvement of genes related to innate and specific immunity, and replicated examples of interaction of genes and the environment. New genes identified through positional cloning studies, such as ADAM33, revived the interest in the airway epithelium and mesenchyme as important structural cells in asthma. Most genome-wide association studies discovered genes related to asthma that functions at the interface of airway structural cells and inflammation, such as IL33, IL1RL1 and TSLP. Epigenetics refers to heritable changes in gene expression without changes in DNA sequence, and includes DNA methylation, histone modifications and microRNAs. Several environmental factors known to be relevant in asthma may influence epigenetic modifications, however, the specific role of epigenetics in asthma is not clear. The ultimate goal of research in (epi)genetics of asthma is to identify susceptible subjects, and to contribute to (preventative) interventions.

Published
2012

27. Partial Response to Sorafenib in a Child With a Myeloid/Lymphoid Neoplasm, Eosinophilia, and a ZMYM2-FLT3 Fusion

Author

Munthe-Kaas, Monica C., Forthun, Rakel B., Brendehaug, Atle, Eek, Anette K., Høysæter, Trude, Osnes, Liv T.N., Prescott, Trine, Spetalen, Signe, and Hovland, Randi

Abstract

Supplemental Digital Content is available in the text.Dysregulated tyrosine kinases in myeloid/lymphoid neoplasms with eosinophilia are rare, but do occur in children. To increase awareness of this diagnosis, we present a child who was diagnosed after a 3-year disease history. The patient was initially treated according to a T-cell lymphoblastic lymphoma protocol, but genetic analyses at recurrence revealed microdeletions resulting in an in-frame fusion of ZMYM2and FLT3. Treatment with sorafenib, an FLT3 tyrosine kinase inhibitor, rapidly resulted in significant reduction of lymphadenopathy and normalization of white blood cell and eosinophil counts. At 17 months of treatment, he remains in complete hematological, but not molecular remission.

Published
2024
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29. MoBa and the International Childhood Cancer Cohort Consortium (I4C)

Author

Dwyer, Terence, primary, Tikellis, Gabriella, additional, Ghantous, Akram, additional, Lemeshow, Stanley, additional, Håberg, Siri E., additional, Olsen, Jørn, additional, Paltiel, Ora, additional, Golding, Jean, additional, Linet, Martha S., additional, Herceg, Zdenko, additional, Munthe-Kaas, Monica C., additional, and Stoltenberg, Camilla, additional

Published
2014
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30. Alpha-nicotinic acetylcholine receptor and tobacco smoke exposure: Effects on bronchial hyperresponsiveness in children

Author

Torjussen, Tale M., primary, Lødrup Carlsen, Karin C., additional, Munthe-Kaas, Monica C., additional, Mowinckel, Petter, additional, Carlsen, Kai-Håkon, additional, Helms, Peter J., additional, Gerritsen, Jorrit, additional, Whyte, Moira K., additional, Lenney, Warren, additional, Undlien, Dag E., additional, Shianna, Kevin V., additional, Zhu, Guohua, additional, and Pillai, Sreekumar G., additional

Published
2011
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32. 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 I. A., 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
3. Good health

33. Alpha-nicotinic acetylcholine receptor and tobacco smoke exposure: Effects on bronchial hyperresponsiveness in children

Author

Torjussen, Tale M., Carlsen, Karin C. Lodrup, Munthe-Kaas, Monica C., Mowinckel, Petter, Carlsen, Kai-Hakon, Helms, Peter J., Gerritsen, Jorrit, Whyte, Moira K., Lenney, Warren, Undlien, Dag E., Shianna, Kevin V., Zhu, Guohua, and Pillai, Sreekumar G.

Subjects
RISK, bronchial hyperresponsiveness, BIRTH, genetic analysis, ASSOCIATION, asthma, association study, OBSTRUCTIVE PULMONARY-DISEASE, respiratory tract diseases, LUNG-CANCER, CHRNA3, SNP rs8034191, SUBUNIT, cohort study, METHACHOLINE, SUSCEPTIBILITY LOCUS, POLYMORPHISMS
Abstract

Background: The CHRNA 3 and 5 genes on chromosome 15 encode the alpha subunits of the nicotinic acetylcholine receptor, mediating airway cholinergic activity. Polymorphisms are associated with cigarette smoking, chronic obstructive pulmonary disease, and lung cancer. Aims: To determine possible associations between CHRNA 3/5 SNP rs8034191 and asthma or lung function in children in one local and one replicate multinational population, and assess if tobacco smoke modified the associations. Materials and methods: The rs8034191 SNP genotyped in 551 children from the environment and childhood asthma (ECA) birth cohort study in Oslo, Norway, and in 516 families from six European centers [the Genetics of Asthma International Network (GAIN) study] was tested for genotypic or allelic associations to current or history of asthma, allergic sensitization (= one positive skin prick tests), bronchial hyperresponsiveness (BHR), and lung function (FEV1% of predicted and FEV1/FVC ratio over/ below the 5th percentile). Results: Although the TT and CT genotypes at SNP rs 8034191 were overall significantly associated with BHR (OR = 3.9, 95% CI 1.510.0, p = 0.005), stratified analyses according to exposure to maternal smoking in-utero or indoor smoking at 10 yrs of age showed significant association (OR = 4.4, 95% CI 1.512.6, p = 0.006 and OR 5.6, 95% CI 1.718.5, p = 0.004, respectively) only in the non-exposed and not in exposed children. The SNPBHR association was replicated in the non-tobacco-smoke-exposed subjects in one of the GAIN centers (BHR associated with the T allele (p = 0.034)), but not in the collated GAIN populations. Asthma, allergic sensitization, and lung function were not associated with the rs8034191 alleles. Conclusion: An interaction between tobacco smoke exposure and a CHRNA3/5 polymorphism was found for BHR in children, but CHRNA3/5 was not associated with asthma or lung function.

34. Pediatric spinal high-grade glioma in the pediatric precision oncology registry INFORM: Identification of potential therapeutic targets.

Author

Pfaff E, Schramm K, Blattner-Johnson M, Jones BC, Stark S, Balasubramanian GP, Previti C, Autry RJ, Fiesel P, Sahm F, Reuss D, von Deimling A, van Tilburg CM, Pajtler KW, Milde T, Dirksen U, Kramm CM, von Bueren AO, Munthe-Kaas MC, Øra I, Pfister SM, Witt O, and Jones DTW

Abstract

Background: High-grade glioma (HGG) of the spinal cord constitutes rare tumors in the pediatric population. Knowledge of the molecular profile of this pediatric HGG (pedHGG) subgroup is limited and the clinical outcome is poor. Therefore, the aim of this study is to provide more profound investigations of molecular characteristics and clinical features of these tumors., Methods: Between January 2015 and October 2023, 17 spinal tumors with HGG histology were analyzed by the Individualized Therapy For Relapsed Malignancies in Childhood (INFORM) precision oncology registry. Comprehensive molecular profiling (including next-generation sequencing approaches and DNA methylation analysis) was performed. Clinical data provided by the treating centers were evaluated regarding treatment approaches and outcomes., Results: Subgroup classification based on DNA methylation analysis revealed molecular HGG subgroups in 12/17 cases, while 2/17 were classified as molecular low-grade glioma (LGG) and 3/17 were not unequivocally classifiable. Typical genetic alterations described in pedHGG usually presenting at other localizations were also present in the counterparts located in the spinal cohort. Alterations that might serve as a promising target for personalized therapy approaches were identified in a subset of tumors., Conclusion: With this cohort of 12 molecularly confirmed spinal pedHGG cases, we provide a compilation of genomic as well as clinical features of this rare subgroup, contributing to a better understanding and eventually to future treatment approaches., Competing Interests: A.v.D.: shareholder in Heidelberg Epignostix. C.M.v.T.: advisory board in Alexion, Bayer, Novartis, and Roche. T.M.: research grants from The Brain Tumor Charity, Biomed Valley Discoveries, and Day One Biopharmaceuticals. C.M.K.: advisory board in Boehringer Ingelheim; contracts for clinical trials: Blueprint Rover and Novartis. A.O.v.B: advisory board in Alexion and Novartis. S.M.P: advisory board in BioSkryb; cofounder & shareholder in Heidelberg Epignostix. O.W.: advisory board in Novartis; contracts for clinical trials: Novartis, Bayer, AstraZeneca, Loxo Janssen, Roche, Day One Biopharmaceuticals, and GSK; consulting fees: Roche, BMS, Day One Biopharmaceuticals, Ipsen, and Novartis; receipt of drugs for preclinical testing: BMS, JS Innopharm, Kronos Bio, and ProLynx. D.T.W.J.: advisory board in Day One Biopharmaceuticals; co-founder & shareholder in Heidelberg Epignostix., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Published
2024
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