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1. Maternal age is related to offspring DNA methylation: A meta‐analysis of results from the PACE consortium

Author

Yeung, Edwina, Biedrzycki, Richard J, Herrera, Laura C Gómez, Issarapu, Prachand, Dou, John, Marques, Irene Fontes, Mansuri, Sohail Rafik, Page, Christian Magnus, Harbs, Justin, Khodasevich, Dennis, Poisel, Eric, Niu, Zhongzheng, Allard, Catherine, Casey, Emma, Berstein, Fernanda Morales, Mancano, Giulia, Elliott, Hannah R, Richmond, Rebecca, He, Yiyan, Ronkainen, Justiina, Sebert, Sylvain, Bell, Erin M, Sharp, Gemma, Mumford, Sunni L, Schisterman, Enrique F, Chandak, Giriraj R, Fall, Caroline HD, Sahariah, Sirazul A, Silver, Matt J, Prentice, Andrew M, Bouchard, Luigi, Domellof, Magnus, West, Christina, Holland, Nina, Cardenas, Andres, Eskenazi, Brenda, Zillich, Lea, Witt, Stephanie H, Send, Tabea, Breton, Carrie, Bakulski, Kelly M, Fallin, M Daniele, Schmidt, Rebecca J, Stein, Dan J, Zar, Heather J, Jaddoe, Vincent WV, Wright, John, Grazuleviciene, Regina, Gutzkow, Kristine Bjerve, Sunyer, Jordi, Huels, Anke, Vrijheid, Martine, Harlid, Sophia, London, Stephanie, Hivert, Marie‐France, Felix, Janine, Bustamante, Mariona, and Guan, Weihua

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Prevention, Human Genome, Clinical Research, Women's Health, Aging, Pediatric, Good Health and Well Being, DNA Methylation, Humans, Female, Maternal Age, Infant, Newborn, Child, Adult, Male, Child, Preschool, CpG Islands, Pregnancy, aging, child, DNA methylation, melatonin, receptor, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR

Published
2024

2. 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 HL, 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 PM, Yang, Ivana V, Dabelea, Dana, Fossati, Serena, Zenclussen, Ana C, Herberth, Gunda, Magnus, Maria, Håberg, Siri E, London, Stephanie J, Munthe-Kaas, Monica Cheng, 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 WV, Järvelin, Marjo-Riitta, Kantomaa, Marko, Felix, Janine F, and Sebert, Sylvain

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Prevention, Nutrition, Women's Health, Maternal Health, Human Genome, Pediatric, Social Determinants of Health, Genetics, Pregnancy, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, 1.1 Normal biological development and functioning, Generic health relevance, Reproductive health and childbirth, Good Health and Well Being, Humans, DNA Methylation, Female, Adolescent, Epigenome, Child, Educational Status, Male, Genome-Wide Association Study, Epigenesis, Genetic, Prenatal Exposure Delayed Effects, Child, Preschool, Infant, Mothers, Infant, Newborn, Adult, Academic Success, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
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
2024

3. 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

4. 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

5. A National Surveillance Survey on Noncommunicable Disease Risk Factors: Suriname Health Study Protocol

Author

Krishnadath, Ingrid SK, Smits, Christel CF, Jaddoe, Vincent WV, Hofman, Albert, and Toelsie, Jerry R

Subjects
Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundNoncommunicable diseases (NCDs) are the leading cause of death in low- and middle-income countries. Therefore, the surveillance of risk factors has become an issue of major importance for planning and implementation of preventive measures. Unfortunately, in these countries data on NCDs and their risk factors are limited. This also prevails in Suriname, a middle-income country of the Caribbean, with a multiethnic/multicultural population living in diverse residential areas. For these reasons, “The Suriname Health Study” was designed. ObjectiveThe main objective of this study is to estimate the prevalence of NCD risk factors, including metabolic syndrome, hypertension, and diabetes in Suriname. Differences between specific age groups, sexes, ethnic groups, and geographical areas will be emphasized. In addition, risk groups will be identified and targeted actions will be designed and evaluated. MethodsIn this study, several methodologies were combined. A stratified multistage cluster sample was used to select the participants of 6 ethnic groups (Hindustani, Creole, Javanese, Maroon, Chinese, Amerindians, and mixed) divided into 5 age groups (between 15 and 65 years) who live in urban/rural areas or the hinterland. A standardized World Health Organization STEPwise approach to surveillance questionnaire was adapted and used to obtain information about demographic characteristics, lifestyle, and risk factors. Physical examinations were performed to measure blood pressure, height, weight, and waist circumference. Biochemical analysis of collected blood samples evaluated the levels of glucose, high-density-lipoprotein cholesterol, total cholesterol, and triglycerides. Statistical analysis will be used to identify the burden of modifiable and unmodifiable risk factors in the aforementioned subgroups. Subsequently, tailor-made interventions will be prepared and their effects will be evaluated. ResultsThe data as collected allow for national inference and valid analysis of the age, sex, and ethnicity subgroups in the Surinamese population. A publication of the basic survey results is anticipated in mid-2015. Secondary results on the effect of targeted lifestyle interventions are anticipated in late 2017. ConclusionsUsing the data collected in this study, the national prevalence of NCD risk factors will be approximated and described in a diverse population. This study is an entry point for formulating the structure of NCD prevention and surveillance.

Published
2015
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7. 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

8. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author

Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I, Raygoza Garay, Juan Antonio, Finnicum, Casey T, Liu, Xingrong, Zhernakova, Daria V, Bonder, Marc Jan, Hansen, Tue H, Frost, Fabian, Rühlemann, Malte C, Turpin, Williams, Moon, Jee-Young, Kim, Han-Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A, Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D, Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T, Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I, Burk, Robert D, Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E, van Duijn, Cornelia M, Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A, Ijzerman, Richard G, Jackson, Matthew A, Jaddoe, Vincent WV, Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J, Lieb, Wolfgang, Lusis, Aldons J, Masclee, Ad AM, Moll, Henriette A, Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J, Steves, Claire J, Thorsen, Jonathan, Timpson, Nicholas J, Tito, Raul Y, Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H, Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U, Weissbrod, Omer, Westra, Harm-Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy MAE, Arias Vasquez, Alejandro, de Geus, Eco JC, Meyer, Katie A, Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung-Lae, Kaplan, Robert C, Spector, Tim D, Uitterlinden, Andre G, Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M, Franke, Lude, Sanna, Serena, D’Amato, Mauro, and Pedersen, Oluf

Subjects
Microbiology, Biological Sciences, Genetics, Human Genome, Biotechnology, Clinical Research, Digestive Diseases, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Adolescent, Adult, Bifidobacterium, Child, Child, Preschool, Cohort Studies, Female, Gastrointestinal Microbiome, Genetic Variation, Genome-Wide Association Study, Humans, Lactase, Linkage Disequilibrium, Male, Mendelian Randomization Analysis, Metabolism, Quantitative Trait Loci, RNA, Ribosomal, 16S, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P

Published
2021

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

Author

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

Subjects
Biological Sciences, Genetics, Pediatric, Nutrition, Prevention, Human Genome, Obesity, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Cardiovascular, Cancer, Stroke, Oral and gastrointestinal, Adolescent, Body Mass Index, Child, Child, Preschool, CpG Islands, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Epigenome, Female, Fetal Blood, Humans, Male, Parturition, Pediatric Obesity, Pregnancy, Body mass index, Childhood obesity, DNA methylation, Epigenetics, Clinical Sciences
Abstract

BackgroundDNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.MethodsWe examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.ResultsDNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P

Published
2020

10. Prenatal maternal antidepressants, anxiety, and depression and offspring DNA methylation: epigenome-wide associations at birth and persistence into early childhood

Author

Cardenas, Andres, Faleschini, Sabrina, Cortes Hidalgo, Andrea, Rifas-Shiman, Sheryl L, Baccarelli, Andrea A, DeMeo, Dawn L, Litonjua, Augusto A, Neumann, Alexander, Felix, Janine F, Jaddoe, Vincent WV, El Marroun, Hanan, Tiemeier, Henning, Oken, Emily, Hivert, Marie-France, and Burris, Heather H

Subjects
Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, Conditions Affecting the Embryonic and Fetal Periods, Pediatric, Human Genome, Depression, Mental Health, Genetics, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Mental health, Reproductive health and childbirth, Good Health and Well Being, Adult, Antidepressive Agents, Anxiety, Child, Preschool, DNA Methylation, DNA-Binding Proteins, Epigenesis, Genetic, Female, Fetal Blood, Humans, Infant, Infant, Newborn, Male, Maternal Age, Maternal Exposure, Oligonucleotide Array Sequence Analysis, Pregnancy, Prenatal Exposure Delayed Effects, Prospective Studies, Transcription Factors, Whole Genome Sequencing, Maternal depression, Maternal anxiety, Antidepressants, DNA methylation, Fetal programming, Clinical Sciences, Paediatrics and Reproductive Medicine
Abstract

BACKGROUND:Maternal mood disorders and their treatment during pregnancy may have effects on the offspring epigenome. We aim to evaluate associations of maternal prenatal antidepressant use, anxiety, and depression with cord blood DNA methylation across the genome at birth and test for persistence of associations in early and mid-childhood blood DNA. METHODS:A discovery phase was conducted in Project Viva, a prospective pre-birth cohort study with external replication in an independent cohort, the Generation R Study. In Project Viva, pregnant women were recruited between 1999 and 2002 in Eastern Massachusetts, USA. In the Generation R Study, pregnant women were recruited between 2002 and 2006 in Rotterdam, the Netherlands. In Project Viva, 479 infants had data on maternal antidepressant use, anxiety, depression, and cord blood DNA methylation, 120 children had DNA methylation measured in early childhood (~ 3 years), and 460 in mid-childhood (~ 7 years). In the Generation R Study, 999 infants had data on maternal antidepressants and cord blood DNA methylation. The prenatal antidepressant prescription was obtained from medical records. At-mid pregnancy, symptoms of anxiety and depression were assessed with the Pregnancy-Related Anxiety Scale and the Edinburgh Postnatal Depression Scale in Project Viva and with the Brief Symptom Inventory in the Generation R Study. Genome-wide DNA methylation was measured using the Infinium HumanMethylation450 BeadChip in both cohorts. RESULTS:In Project Viva, 2.9% (14/479) pregnant women were prescribed antidepressants, 9.0% (40/445) experienced high pregnancy-related anxiety, and 8.2% (33/402) reported symptoms consistent with depression. Newborns exposed to antidepressants in pregnancy had 7.2% lower DNA methylation (95% CI, - 10.4, - 4.1; P = 1.03 × 10-8) at cg22159528 located in the gene body of ZNF575, and this association replicated in the Generation R Study (β = - 2.5%; 95% CI - 4.2, - 0.7; P = 0.006). In Project Viva, the association persisted in early (β = - 6.2%; 95% CI - 10.7, - 1.6) but not mid-childhood. We observed cohort-specific associations for maternal anxiety and depression in Project Viva that did not replicate. CONCLUSIONS:The ZNF575 gene is involved in transcriptional regulation but specific functions are largely unknown. Given the widespread use of antidepressants in pregnancy, as well as the effects of exposure to anxiety and depression, implications of potential fetal epigenetic programming by these risk factors and their impacts on development merit further investigation.

Published
2019

11. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria.

Author

Teumer, Alexander, Li, Yong, Ghasemi, Sahar, Prins, Bram P, Wuttke, Matthias, Hermle, Tobias, Giri, Ayush, Sieber, Karsten B, Qiu, Chengxiang, Kirsten, Holger, Tin, Adrienne, Chu, Audrey Y, Bansal, Nisha, Feitosa, Mary F, Wang, Lihua, Chai, Jin-Fang, Cocca, Massimiliano, Fuchsberger, Christian, Gorski, Mathias, Hoppmann, Anselm, Horn, Katrin, Li, Man, Marten, Jonathan, Noce, Damia, Nutile, Teresa, Sedaghat, Sanaz, Sveinbjornsson, Gardar, Tayo, Bamidele O, van der Most, Peter J, Xu, Yizhe, Yu, Zhi, Gerstner, Lea, Ärnlöv, Johan, Bakker, Stephan JL, Baptista, Daniela, Biggs, Mary L, Boerwinkle, Eric, Brenner, Hermann, Burkhardt, Ralph, Carroll, Robert J, Chee, Miao-Li, Chee, Miao-Ling, Chen, Mengmeng, Cheng, Ching-Yu, Cook, James P, Coresh, Josef, Corre, Tanguy, Danesh, John, de Borst, Martin H, De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko PJ, Degenhardt, Frauke, Dittrich, Katalin, Divers, Jasmin, Eckardt, Kai-Uwe, Ehret, Georg, Endlich, Karlhans, Felix, Janine F, Franco, Oscar H, Franke, Andre, Freedman, Barry I, Freitag-Wolf, Sandra, Gansevoort, Ron T, Giedraitis, Vilmantas, Gögele, Martin, Grundner-Culemann, Franziska, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hamet, Pavel, Harris, Tamara B, Hicks, Andrew A, Holm, Hilma, Foo, Valencia Hui Xian, Hwang, Shih-Jen, Ikram, M Arfan, Ingelsson, Erik, Jaddoe, Vincent WV, Jakobsdottir, Johanna, Josyula, Navya Shilpa, Jung, Bettina, Kähönen, Mika, Khor, Chiea-Chuen, Kiess, Wieland, Koenig, Wolfgang, Körner, Antje, Kovacs, Peter, Kramer, Holly, Krämer, Bernhard K, Kronenberg, Florian, Lange, Leslie A, Langefeld, Carl D, Lee, Jeannette Jen-Mai, Lehtimäki, Terho, Lieb, Wolfgang, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M, Liu, Jianjun, and Loeffler, Markus

Subjects
Animals, Humans, Drosophila melanogaster, Albuminuria, Diabetes Mellitus, Genetic Predisposition to Disease, Creatinine, Risk Factors, Chromosome Mapping, Gene Expression Regulation, Meta-Analysis as Topic, Genome-Wide Association Study, Genetic Loci, Phenomics
Abstract

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

Published
2019

12. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.

Author

Liu, Xueping, Helenius, Dorte, Skotte, Line, Beaumont, Robin N, Wielscher, Matthias, Geller, Frank, Juodakis, Julius, Mahajan, Anubha, Bradfield, Jonathan P, Lin, Frederick TJ, Vogelezang, Suzanne, Bustamante, Mariona, Ahluwalia, Tarunveer S, Pitkänen, Niina, Wang, Carol A, Bacelis, Jonas, Borges, Maria C, Zhang, Ge, Bedell, Bruce A, Rossi, Robert M, Skogstrand, Kristin, Peng, Shouneng, Thompson, Wesley K, Appadurai, Vivek, Lawlor, Debbie A, Kalliala, Ilkka, Power, Christine, McCarthy, Mark I, Boyd, Heather A, Marazita, Mary L, Hakonarson, Hakon, Hayes, M Geoffrey, Scholtens, Denise M, Rivadeneira, Fernando, Jaddoe, Vincent WV, Vinding, Rebecca K, Bisgaard, Hans, Knight, Bridget A, Pahkala, Katja, Raitakari, Olli, Helgeland, Øyvind, Johansson, Stefan, Njølstad, Pål R, Fadista, João, Schork, Andrew J, Nudel, Ron, Miller, Daniel E, Chen, Xiaoting, Weirauch, Matthew T, Mortensen, Preben Bo, Børglum, Anders D, Nordentoft, Merete, Mors, Ole, Hao, Ke, Ryckman, Kelli K, Hougaard, David M, Kottyan, Leah C, Pennell, Craig E, Lyytikainen, Leo-Pekka, Bønnelykke, Klaus, Vrijheid, Martine, Felix, Janine F, Lowe, William L, Grant, Struan FA, Hyppönen, Elina, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Muglia, Louis J, Murray, Jeffrey C, Freathy, Rachel M, Werge, Thomas M, Melbye, Mads, Buil, Alfonso, and Feenstra, Bjarke

Subjects
Chromosomes, Human, Pair 2, Fetus, Humans, Premature Birth, Cytokines, Gestational Age, Pregnancy, Polymorphism, Single Nucleotide, Genome, Human, Infant, Newborn, Female, Genome-Wide Association Study, Chromosomes, Human, Pair 2, Polymorphism, Single Nucleotide, Genome, Infant, Newborn
Abstract

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

Published
2019

13. An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

Author

Liu, Jun, Carnero-Montoro, Elena, van Dongen, Jenny, Lent, Samantha, Nedeljkovic, Ivana, Ligthart, Symen, Tsai, Pei-Chien, Martin, Tiphaine C, Mandaviya, Pooja R, Jansen, Rick, Peters, Marjolein J, Duijts, Liesbeth, Jaddoe, Vincent WV, Tiemeier, Henning, Felix, Janine F, Willemsen, Gonneke, de Geus, Eco JC, Chu, Audrey Y, Levy, Daniel, Hwang, Shih-Jen, Bressler, Jan, Gondalia, Rahul, Salfati, Elias L, Herder, Christian, Hidalgo, Bertha A, Tanaka, Toshiko, Moore, Ann Zenobia, Lemaitre, Rozenn N, Jhun, Min A, Smith, Jennifer A, Sotoodehnia, Nona, Bandinelli, Stefania, Ferrucci, Luigi, Arnett, Donna K, Grallert, Harald, Assimes, Themistocles L, Hou, Lifang, Baccarelli, Andrea, Whitsel, Eric A, van Dijk, Ko Willems, Amin, Najaf, Uitterlinden, André G, Sijbrands, Eric JG, Franco, Oscar H, Dehghan, Abbas, Spector, Tim D, Dupuis, Josée, Hivert, Marie-France, Rotter, Jerome I, Meigs, James B, Pankow, James S, van Meurs, Joyce BJ, Isaacs, Aaron, Boomsma, Dorret I, Bell, Jordana T, Demirkan, Ayşe, and van Duijn, Cornelia M

Subjects
Biological Sciences, Genetics, Nutrition, Diabetes, Human Genome, Obesity, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Aged, Aged, 80 and over, Computer Simulation, CpG Islands, DNA Methylation, Diabetes Mellitus, Type 2, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Profiling, Gene Expression Regulation, Genome-Wide Association Study, Glucose, Homeostasis, Humans, Insulin, Male, Metabolic Networks and Pathways, Middle Aged, Polymorphism, Single Nucleotide, Young Adult
Abstract

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.

Published
2019

14. Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis

Author

Voerman, Ellis, Santos, Susana, Golab, Bernadeta Patro, Amiano, Pilar, Ballester, Ferran, Barros, Henrique, Bergström, Anna, Charles, Marie-Aline, Chatzi, Leda, Chevrier, Cécile, Chrousos, George P, Corpeleijn, Eva, Costet, Nathalie, Crozier, Sarah, Devereux, Graham, Eggesbø, Merete, Ekström, Sandra, Fantini, Maria Pia, Farchi, Sara, Forastiere, Francesco, Georgiu, Vagelis, Godfrey, Keith M, Gori, Davide, Grote, Veit, Hanke, Wojciech, Hertz-Picciotto, Irva, Heude, Barbara, Hryhorczuk, Daniel, Huang, Rae-Chi, Inskip, Hazel, Iszatt, Nina, Karvonen, Anne M, Kenny, Louise C, Koletzko, Berthold, Küpers, Leanne K, Lagström, Hanna, Lehmann, Irina, Magnus, Per, Majewska, Renata, Mäkelä, Johanna, Manios, Yannis, McAuliffe, Fionnuala M, McDonald, Sheila W, Mehegan, John, Mommers, Monique, Morgen, Camilla S, Mori, Trevor A, Moschonis, George, Murray, Deirdre, Chaoimh, Carol Ní, Nohr, Ellen A, Andersen, Anne-Marie Nybo, Oken, Emily, Oostvogels, Adriëtte JJM, Pac, Agnieszka, Papadopoulou, Eleni, Pekkanen, Juha, Pizzi, Costanza, Polanska, Kinga, Porta, Daniela, Richiardi, Lorenzo, Rifas-Shiman, Sheryl L, Ronfani, Luca, Santos, Ana C, Standl, Marie, Stoltenberg, Camilla, Thiering, Elisabeth, Thijs, Carel, Torrent, Maties, Tough, Suzanne C, Trnovec, Tomas, Turner, Steve, van Rossem, Lenie, von Berg, Andrea, Vrijheid, Martine, Vrijkotte, Tanja GM, West, Jane, Wijga, Alet, Wright, John, Zvinchuk, Oleksandr, Sørensen, Thorkild IA, Lawlor, Debbie A, Gaillard, Romy, and Jaddoe, Vincent WV

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Nutrition and Dietetics, Reproductive Medicine, Nutrition, Prevention, Pediatric, Clinical Research, Obesity, Oral and gastrointestinal, Stroke, Reproductive health and childbirth, Cardiovascular, Generic health relevance, Metabolic and endocrine, Cancer, Australia, Body Mass Index, Cohort Studies, Data Analysis, Europe, Female, Gestational Weight Gain, Humans, North America, Overweight, Pediatric Obesity, Pregnancy, Risk Factors, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundMaternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.Methods and findingsWe conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations.ConclusionsIn this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

Published
2019

15. Gestational weight gain charts for different body mass index groups for women in Europe, North America, and Oceania

Author

Santos, Susana, Eekhout, Iris, Voerman, Ellis, Gaillard, Romy, Barros, Henrique, Charles, Marie-Aline, Chatzi, Leda, Chevrier, Cécile, Chrousos, George P, Corpeleijn, Eva, Costet, Nathalie, Crozier, Sarah, Doyon, Myriam, Eggesbø, Merete, Fantini, Maria Pia, Farchi, Sara, Forastiere, Francesco, Gagliardi, Luigi, Georgiu, Vagelis, Godfrey, Keith M, Gori, Davide, Grote, Veit, Hanke, Wojciech, Hertz-Picciotto, Irva, Heude, Barbara, Hivert, Marie-France, Hryhorczuk, Daniel, Huang, Rae-Chi, Inskip, Hazel, Jusko, Todd A, Karvonen, Anne M, Koletzko, Berthold, Küpers, Leanne K, Lagström, Hanna, Lawlor, Debbie A, Lehmann, Irina, Lopez-Espinosa, Maria-Jose, Magnus, Per, Majewska, Renata, Mäkelä, Johanna, Manios, Yannis, McDonald, Sheila W, Mommers, Monique, Morgen, Camilla S, Moschonis, George, Murínová, Ľubica, Newnham, John, Nohr, Ellen A, Andersen, Anne-Marie Nybo, Oken, Emily, Oostvogels, Adriëtte JJM, Pac, Agnieszka, Papadopoulou, Eleni, Pekkanen, Juha, Pizzi, Costanza, Polanska, Kinga, Porta, Daniela, Richiardi, Lorenzo, Rifas-Shiman, Sheryl L, Roeleveld, Nel, Santa-Marina, Loreto, Santos, Ana C, Smit, Henriette A, Sørensen, Thorkild IA, Standl, Marie, Stanislawski, Maggie, Stoltenberg, Camilla, Thiering, Elisabeth, Thijs, Carel, Torrent, Maties, Tough, Suzanne C, Trnovec, Tomas, van Gelder, Marleen MHJ, van Rossem, Lenie, von Berg, Andrea, Vrijheid, Martine, Vrijkotte, Tanja GM, Zvinchuk, Oleksandr, van Buuren, Stef, and Jaddoe, Vincent WV

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Health Sciences, Conditions Affecting the Embryonic and Fetal Periods, Pediatric, Nutrition, Obesity, Clinical Research, Prevention, Perinatal Period - Conditions Originating in Perinatal Period, Metabolic and endocrine, Reproductive health and childbirth, Good Health and Well Being, Adult, Body Mass Index, Europe, Female, Gestational Weight Gain, Humans, North America, Oceania, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Risk Factors, Weight gain, Charts, References, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundGestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies.MethodsWe used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape.ResultsWe observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications.ConclusionsGestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

Published
2018

16. Influence of maternal obesity on the association between common pregnancy complications and risk of childhood obesity: an individual participant data meta-analysis

Author

Golab, Bernadeta Patro, Santos, Susana, Voerman, Ellis, Lawlor, Debbie A, Jaddoe, Vincent WV, Gaillard, Romy, Authors, MOCO Study Group, Barros, Henrique, Bergström, Anna, Charles, Marie-Aline, Chatzi, Leda, Chevrier, Cécile, Chrousos, George P, Corpeleijn, Eva, Costet, Nathalie, Crozier, Sarah, Devereux, Graham, Eggesbø, Merete, Ekström, Sandra, Fantini, Maria P, Farchi, Sara, Forastiere, Francesco, Georgiu, Vagelis, Godfrey, Keith M, Gori, Davide, Hanke, Wojciech, Hertz-Picciotto, Irva, Heude, Barbara, Hryhorczuk, Daniel, Inskip, Hazel, Ibarluzea, Jesus, Kenny, Louise C, Küpers, Leanne K, Lagström, Hanna, Lehmann, Irina, Lenters, Virissa, Llop, Sabrina Llop, Magnus, Per, Majewska, Renata, Mäkelä, Johanna, Manios, Yannis, McAuliffe, Fionnuala M, McDonald, Sheila W, Mehegan, John, Mommers, Monique, Morgen, Camilla S, Moschonis, George, Murray, Deirdre, Chaoimh, Carol Ní, Nøhr, Ellen A, Andersen, Anne-Marie Nybo, Oken, Emily, Oostvogels, Adriëtte JJM, Pac, Agnieszka, Papadopoulou, Eleni, Pizzi, Costanza, Polanska, Kinga, Porta, Daniela, Richiardi, Lorenzo, Rifas-Shiman, Sheryl L, Rusconi, Franca, Santos, Ana C, Smit, Henriette A, Sørensen, Thorkild IA, Standl, Marie, Stoltenberg, Camilla, Sunyer, Jordi, Taylor, Michelle, Thiering, Elisabeth, Thijs, Carel, Torrent, Maties, Tough, Suzanne C, Trnovec, Tomas, Turner, Steve, van Rossem, Lenie, von Berg, Andrea, Vrijheid, Martine, Vrijkotte, Tanja, West, Jane, Wright, John, and Zvinchuk, Oleksandr

Subjects
Nutrition, Contraception/Reproduction, Pediatric, Obesity, Prevention, Clinical Research, Cardiovascular, Perinatal Period - Conditions Originating in Perinatal Period, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Reproductive health and childbirth, Adolescent, Animals, Body Mass Index, Child, Child, Preschool, Diabetes, Gestational, Europe, Female, Humans, Hypertension, Pregnancy-Induced, Life Style, North America, Pediatric Obesity, Pre-Eclampsia, Pregnancy, Pregnancy Complications, Risk Factors, MOCO Study Group Authors
Abstract

BackgroundGestational diabetes and gestational hypertensive disorders are associated with offspring obesity, but the role of maternal adiposity in these associations remains unclear. We aimed to investigate whether these pregnancy complications affect the odds of offspring obesity independently of maternal obesity.MethodsWe did an individual participant data (IPD) meta-analysis of mother-offspring pairs from prospective birth cohort studies that had IPD on mothers with singleton liveborn children born from 1989 onwards and had information available about maternal gestational diabetes, gestational hypertension or pre-eclampsia, and childhood body-mass index (BMI). We applied multilevel mixed-effects models to assess associations of gestational diabetes, gestational hypertension, and pre-eclampsia with BMI SD scores and the odds of overweight and obesity throughout childhood, adjusting for lifestyle characteristics (offspring's sex, maternal age, educational level, ethnicity, parity, and smoking during pregnancy). We then explored the extent to which any association was explained by maternal pre-pregnancy or early-pregnancy BMI.Findings160 757 mother-offspring pairs from 34 European or North American cohorts were analysed. Compared with uncomplicated pregnancies, gestational diabetes was associated with increased odds of overweight or obesity throughout childhood (odds ratio [OR] 1·59 [95% CI 1·36 to 1·86] for early childhood [age 2·0-4·9 years], 1·41 [1·26 to 1·57] for mid childhood [5·0-9·9 years], and 1·32 [0·97 to 1·78] for late childhood [10·0-17·9 years]); however, these associations attenuated towards the null following adjustment for maternal BMI (OR 1·35 [95% CI 1·15 to 1·58] for early childhood, 1·12 [1·00 to 1·25] for mid childhood, and 0·96 [0·71 to 1·31] for late childhood). Likewise, gestational hypertension was associated with increased odds of overweight throughout childhood (OR 1·19 [95% CI 1·01 to 1·39] for early childhood, 1·23 [1·15 to 1·32] for mid childhood, and 1·49 [1·30 to 1·70] for late childhood), but additional adjustment for maternal BMI largely explained these associations (1·01 [95% CI 0·86 to 1·19] for early childhood, 1·02 [0·95 to 1·10] for mid childhood, and 1·18 [1·03 to 1·36] for late childhood). Pre-eclampsia was associated with decreased BMI in early childhood only (difference in BMI SD score -0·05 SD score [95% CI -0·09 to -0·01]), and this association strengthened following additional adjustment for maternal BMI.InterpretationAlthough lowering maternal risk of gestational diabetes, gestational hypertension, and pre-eclampsia is important in relation to maternal and fetal pregnancy outcomes, such interventions are unlikely to have a direct impact on childhood obesity. Preventive strategies for reducing childhood obesity should focus on maternal BMI rather than on pregnancy complications.FundingEU's Horizon 2020 research and innovation programme (LifeCycle Project).

Published
2018

17. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Author

Waage, Johannes, Standl, Marie, Curtin, John A, Jessen, Leon E, Thorsen, Jonathan, Tian, Chao, Schoettler, Nathan, The 23andMe Research Team, AAGC collaborators, Flores, Carlos, Abdellaoui, Abdel, Ahluwalia, Tarunveer S, Alves, Alexessander C, Amaral, Andre FS, Antó, Josep M, Arnold, Andreas, Barreto-Luis, Amalia, Baurecht, Hansjörg, van Beijsterveldt, Catharina EM, Bleecker, Eugene R, Bonàs-Guarch, Sílvia, Boomsma, Dorret I, Brix, Susanne, Bunyavanich, Supinda, Burchard, Esteban G, Chen, Zhanghua, Curjuric, Ivan, Custovic, Adnan, den Dekker, Herman T, Dharmage, Shyamali C, Dmitrieva, Julia, Duijts, Liesbeth, Ege, Markus J, Gauderman, W James, Georges, Michel, Gieger, Christian, Gilliland, Frank, Granell, Raquel, Gui, Hongsheng, Hansen, Torben, Heinrich, Joachim, Henderson, John, Hernandez-Pacheco, Natalia, Holt, Patrick, Imboden, Medea, Jaddoe, Vincent WV, Jarvelin, Marjo-Riitta, Jarvis, Deborah L, Jensen, Kamilla K, Jónsdóttir, Ingileif, Kabesch, Michael, Kaprio, Jaakko, Kumar, Ashish, Lee, Young-Ae, Levin, Albert M, Li, Xingnan, Lorenzo-Diaz, Fabian, Melén, Erik, Mercader, Josep M, Meyers, Deborah A, Myers, Rachel, Nicolae, Dan L, Nohr, Ellen A, Palviainen, Teemu, Paternoster, Lavinia, Pennell, Craig E, Pershagen, Göran, Pino-Yanes, Maria, Probst-Hensch, Nicole M, Rüschendorf, Franz, Simpson, Angela, Stefansson, Kari, Sunyer, Jordi, Sveinbjornsson, Gardar, Thiering, Elisabeth, Thompson, Philip J, Torrent, Maties, Torrents, David, Tung, Joyce Y, Wang, Carol A, Weidinger, Stephan, Weiss, Scott, Willemsen, Gonneke, Williams, L Keoki, Ober, Carole, Hinds, David A, Ferreira, Manuel A, Bisgaard, Hans, Strachan, David P, and Bønnelykke, Klaus

Subjects
Biological Sciences, Genetics, Prevention, Allergic Rhinitis (Hay Fever), Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Allergens, Case-Control Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genome-Wide Association Study, HLA Antigens, Humans, Phenotype, Rhinitis, Allergic, Risk, 23andMe Research Team, AAGC collaborators, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

Published
2018

19. 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

20. 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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21. A genome-wide association meta-analysis identifies new childhood obesity loci

Author

Bradfield, Jonathan P, Taal, H Rob, Timpson, Nicholas J, Scherag, Andre, Lecoeur, Cecile, Warrington, Nicole M, Hypponen, Elina, Holst, Claus, Valcarcel, Beatriz, Thiering, Elisabeth, Salem, Rany M, Schumacher, Fredrick R, Cousminer, Diana L, Sleiman, Patrick MA, Zhao, Jianhua, Berkowitz, Robert I, Vimaleswaran, Karani S, Jarick, Ivonne, Pennell, Craig E, Evans, David M, St Pourcain, Beate, Berry, Diane J, Mook-Kanamori, Dennis O, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, van Duijn, Cornelia M, van der Valk, Ralf JP, de Jongste, Johan C, Postma, Dirkje S, Boomsma, Dorret I, Gauderman, W James, Hassanein, Mohamed T, Lindgren, Cecilia M, Magi, Reedik, Boreham, Colin AG, Neville, Charlotte E, Moreno, Luis A, Elliott, Paul, Pouta, Anneli, Hartikainen, Anna-Liisa, Li, Mingyao, Raitakari, Olli, Lehtimaki, Terho, Eriksson, Johan G, Palotie, Aarno, Dallongeville, Jean, Das, Shikta, Deloukas, Panos, McMahon, George, Ring, Susan M, Kemp, John P, Buxton, Jessica L, Blakemore, Alexandra IF, Bustamante, Mariona, Guxens, Monica, Hirschhorn, Joel N, Gillman, Matthew W, Kreiner-Moller, Eskil, Bisgaard, Hans, Gilliland, Frank D, Heinrich, Joachim, Wheeler, Eleanor, Barroso, Ines, O'Rahilly, Stephen, Meirhaeghe, Aline, Sorensen, Thorkild IA, Power, Chris, Palmer, Lyle J, Hinney, Anke, Widen, Elisabeth, Farooqi, I Sadaf, McCarthy, Mark I, Froguel, Philippe, Meyre, David, Hebebrand, Johannes, Jarvelin, Marjo-Riitta, Jaddoe, Vincent WV, Smith, George Davey, Hakonarson, Hakon, and Grant, Struan FA

Subjects
Biological Sciences, Genetics, Pediatric, Nutrition, Obesity, Human Genome, Metabolic and endocrine, Oral and gastrointestinal, Stroke, Cancer, Cardiovascular, Adolescent, Adult, Body Mass Index, Case-Control Studies, Genetic Loci, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Young Adult, Early Growth Genetics Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (

Published
2012

22. Association of light-to-moderate alcohol drinking in pregnancy with preterm birth and birth weight: elucidating bias by pooling data from nine European cohorts

Author

Strandberg-Larsen, Katrine, Poulsen, Gry, Bech, Bodil Hammer, Chatzi, Leda, Cordier, Sylvaine, Dale, Maria Teresa Grønning, Fernandez, Marieta, Henriksen, Tine Brink, Jaddoe, Vincent WV, Kogevinas, Manolis, Kruithof, Claudia J., Lindhard, Morten Søndergaard, Magnus, Per, Nohr, Ellen Aagaard, Richiardi, Lorenzo, Rodriguez-Bernal, Clara L., Rouget, Florence, Rusconi, Franca, Vrijheid, Martine, and Andersen, Anne-Marie Nybo

Published
2017

25. 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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26. 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

36. Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies

Author

Leventakou, Vasiliki, Roumeliotaki, Theano, Martinez, David, Barros, Henrique, Brantsaeter, Anne-Lise, Casas, Maribel, Charles, Marie-Aline, Cordier, Sylvaine, Eggesbø, Merete, van Eijsden, Manon, Forastiere, Francesco, Gehring, Ulrike, Govarts, Eva, Halldórsson, Thorhallur I, Hanke, Wojciech, Haugen, Margaretha, Heppe, Denise HM, Heude, Barbara, Inskip, Hazel M, Jaddoe, Vincent WV, Jansen, Maria, Kelleher, Cecily, Meltzer, Helle Margrete, Merletti, Franco, Moltó-Puigmartí, Carolina, Mommers, Monique, Murcia, Mario, Oliveira, Andreia, Olsen, Sjúrður F, Pele, Fabienne, Polanska, Kinga, Porta, Daniela, Richiardi, Lorenzo, Robinson, Siân M, Stigum, Hein, Strøm, Marin, Sunyer, Jordi, Thijs, Carel, Viljoen, Karien, Vrijkotte, Tanja GM, Wijga, Alet H, Kogevinas, Manolis, Vrijheid, Martine, and Chatzi, Leda

Published
2014
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37. 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, Cheng Munthe-Kaas, Monica, Corpeleijn, Eva, Czamara, Darina, Dabelea, Dana, Davey Smith, George, 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, Starling, Anne P, Sunyer, Jordi, Taylor, Jack A, Tiemeier, Henning, Ullemar, Vilhelmina, Vafeiadi, Marina, Van Ijzendoorn, Marinus H, Vonk, Judith M, Vriens, Annette, Vrijheid, Martine, Wang, Pei, Wiemels, Joseph L, Wilcox, Allen J, Wright, Rosalind J, Xu, Cheng-Jian, Xu, Zongli, Yang, Ivana V, Yousefi, Paul, Zhang, Hongmei, Zhang, Weiming, Zhao, Shanshan, Agha, Golareh, Relton, Caroline L, Jaddoe, Vincent WV, and London, Stephanie J

Published
2018
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39. Associations of maternal urinary bisphenol and phthalate concentrations with offspring reproductive development

Author

Blaauwendraad, Sophia M., Jaddoe, Vincent WV, Santos, Susana, Kannan, Kurunthachalam, Dohle, Gert R., Trasande, Leonardo, Gaillard, Romy, Blaauwendraad, Sophia M., Jaddoe, Vincent WV, Santos, Susana, Kannan, Kurunthachalam, Dohle, Gert R., Trasande, Leonardo, and Gaillard, Romy

Abstract

Fetal exposure to bisphenols and phthalates may influence development of the reproductive system. In a population-based, prospective cohort study of 1059 mother-child pairs, we examined the associations of maternal gestational urinary bisphenols and phthalates concentrations with offspring reproductive development from infancy until 13 years. We measured urinary bisphenol and phthalate concentrations in each trimester. We obtained information on cryptorchidism or hypospadias after birth from medical records. At 9.7 years, we measured testicular and ovarian volume by MRI. At 13.5 years, we measured child Tanner stages and menstruation through questionnaire. We performed linear or logistic regression models for boys and girls to assess the associations of maternal urinary average and trimester-specific bisphenols and phthalates with child reproductive outcomes. Next, to further explore potential synergistic or additive effects of exposures together, we performed mixed exposure models using a quantile g computation approach. Models were adjusted for maternal age, ethnicity, body-mass index, education, parity, energy intake, smoking and alcohol use, and child's gestational age at birth, birthweight and body-mass index. In boys, no associations of maternal gestational phthalate or bisphenol with offspring cryptorchidism and hypospadias were found. Higher maternal high-molecular-weight phthalate and total bisphenol, but not phthalic acid or low-molecular-weight phthalate, were associated with larger child testicular volume at 10 years. Higher maternal phthalic acid and total bisphenol were associated with earlier genital and pubic hair development at 13 years, respectively (p-values<0.05). In girls, we found no associations of maternal urinary bisphenol and phthalate with ovarian volume or menstrual age. Only higher maternal urinary high-molecular-weight phthalate was associated with earlier pubic hair development at 13 years (p-values <0.05). Higher mixture expo

Published
2022

41. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author

Haworth, Simon, Shapland, Chin Yang, Hayward, Caroline, Prins, Bram P, Felix, Janine F, Medina-Gomez, Carolina, Rivadeneira, Fernando, Wang, Carol, Ahluwalia, Tarunveer S, Vrijheid, Martine, Guxens, Mònica, Sunyer, Jordi, Tachmazidou, Ioanna, Walter, Klaudia, Iotchkova, Valentina, Jackson, Andrew, Cleal, Louise, Huffmann, Jennifer, Min, Josine L, Sass, Lærke, Timmers, Paul RHJ, UK10K Consortium, Davey Smith, George, Fisher, Simon E, Wilson, James F, Cole, Tim J, Fernandez-Orth, Dietmar, Bønnelykke, Klaus, Bisgaard, Hans, Pennell, Craig E, Jaddoe, Vincent WV, Dedoussis, George, Timpson, Nicholas, Zeggini, Eleftheria, Vitart, Veronique, St Pourcain, Beate, Haworth, Simon [0000-0001-7793-7326], Shapland, Chin Yang [0000-0002-5797-1241], Hayward, Caroline [0000-0002-9405-9550], Felix, Janine F [0000-0002-9801-5774], Medina-Gomez, Carolina [0000-0001-7999-5538], Rivadeneira, Fernando [0000-0001-9435-9441], Wang, Carol [0000-0002-4301-3974], Ahluwalia, Tarunveer S [0000-0002-7464-3354], Jackson, Andrew [0000-0002-8739-2646], Huffmann, Jennifer [0000-0002-9672-2491], Min, Josine L [0000-0003-4456-9824], Timmers, Paul RHJ [0000-0002-5197-1267], Davey Smith, George [0000-0002-1407-8314], Fisher, Simon E [0000-0002-3132-1996], Wilson, James F [0000-0001-5751-9178], Cole, Tim J [0000-0001-5711-8200], Fernandez-Orth, Dietmar [0000-0002-1237-3192], Bønnelykke, Klaus [0000-0003-2003-1018], Bisgaard, Hans [0000-0003-4131-7592], Jaddoe, Vincent WV [0000-0003-2939-0041], Zeggini, Eleftheria [0000-0003-4238-659X], Vitart, Veronique [0000-0002-4991-3797], St Pourcain, Beate [0000-0002-4680-3517], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Adolescent, Cephalometry, LD SCORE REGRESSION, Science, White People, GENETIC ARCHITECTURE, Gene Frequency, IMPUTATION, Humans, GWAS, RNA, Messenger, GENOME-WIDE ASSOCIATION, BRAIN, Child, lcsh:Science, Alleles, Aged, Aged, 80 and over, Genome, Human, HERITABILITY, Skull, Gene Expression Regulation, Developmental, Genetic Variation, COMMON VARIANTS, Middle Aged, Genetic Loci, GROWTH, Female, lcsh:Q, WEIGHT, Tumor Suppressor Protein p53
Abstract

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.

Published
2019

42. Association of assisted reproductive technology with long-term offspring cardiometabolic health: a multi-cohort study

Author

Elhakeem, Ahmed, primary, Taylor, Amy E, additional, Inskip, Hazel M, additional, Huang, Jonathan, additional, Mansell, Toby, additional, Rodrigues, Carina, additional, Asta, Federica, additional, Blaauwendraad, Sophie M, additional, Haberg, Siri E, additional, Halliday, Jane, additional, Harskamp-van Ginkel, Margreet W, additional, He, Jian-Rong, additional, Jaddoe, Vincent WV, additional, Lewis, Sharon, additional, Maher, Gillian M, additional, Manios, Yannis, additional, McCarthy, Fergus P, additional, Reiss, Irwin KM, additional, Rusconi, Franca, additional, Salika, Theodosia, additional, Tafflet, Muriel, additional, Qiu, Xiu, additional, Asvold, Bjorn O, additional, Burgner, David, additional, Chan, Jerry KY, additional, Gagliardi, Luigi, additional, Gaillard, Romy, additional, Heude, Barbara, additional, Magnus, Maria C, additional, Moschonis, George, additional, Murray, Deirdre, additional, Nelson, Scott M, additional, Porta, Daniela, additional, Saffery, Richard, additional, Barros, Henrique, additional, Eriksson, Johan G, additional, Vrijkotte, Tanja GM, additional, and Lawlor, Deborah A, additional

Published
2022
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43. Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study

Author

Elhakeem, Ahmed, primary, Ronkainen, Justiina, additional, Mansell, Toby, additional, Lange, Katherine, additional, Mikkola, Tuija, additional, Mishra, Binisha H, additional, Wahab, Rama, additional, Cadman, Tim, additional, Yang, Tiffany, additional, Burgner, David, additional, Eriksson, Johan G, additional, Jarvelin, Marjo-Riitta, additional, Gaillard, Romy, additional, Jaddoe, Vincent WV, additional, Lehtimaki, Terho, additional, Raitakari, Olli T, additional, Saffery, Richard, additional, Wake, Melissa, additional, Wright, John, additional, Sebert, Sylvain, additional, and Lawlor, Deborah A, additional

Published
2022
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48. 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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