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

Author

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

Subjects
PACE, Meta-analysis, Birth season, DNA methylation, Differentially methylated regions (DMR), Latitude, Medicine, Genetics, QH426-470
Abstract

Abstract Background Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. Methods We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1–11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. Results We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values

Published
2023
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2. Comparison of DNA methylation measured by Illumina 450K and EPIC BeadChips in blood of newborns and 14-year-old children

Author

Olivia Solomon, Julie MacIsaac, Hong Quach, Gwen Tindula, Michael S. Kobor, Karen Huen, Michael J. Meaney, Brenda Eskenazi, Lisa F. Barcellos, and Nina Holland

Subjects
450k, epic, 850k, dna methylation, epigenetics, cord blood, children, Genetics, QH426-470
Abstract

Analysis of DNA methylation helps to understand the effects of environmental exposures as well as the role of epigenetics in human health. Illumina, Inc. recently replaced the HumanMethylation450 BeadChip (450K) with the EPIC BeadChip, which nearly doubles the measured CpG sites to >850,000. Although the new chip uses the same underlying technology, it is important to establish if data between the two platforms are comparable within cohorts and for meta-analyses. DNA methylation was assessed by 450K and EPIC using whole blood from newborn (n = 109) and 14-year-old (n = 86) participants of the Center for the Health Assessment of Mothers and Children of Salinas. The overall per-sample correlations were very high (r >0.99), although many individual CpG sites, especially those with low variance of methylation, had lower correlations (median r = 0.24). There was also a small subset of CpGs with large mean methylation β-value differences between platforms, in both the newborn and 14-year datasets. However, estimates of cell type proportion prediction by 450K and EPIC were highly correlated at both ages. Finally, differentially methylated positions between boys and girls replicated very well by both platforms in newborns and older children. These findings are encouraging for application of combined data from EPIC and 450K platforms for birth cohorts and other population studies. These data in children corroborate recent comparisons of the two BeadChips in adults and in cancer cell lines. However, researchers should be cautious when characterizing individual CpG sites and consider independent methods for validation of significant hits.

Published
2018
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3. Dynamics of Methylation of CpG Sites Associated With Systemic Lupus Erythematosus Subtypes in a Longitudinal Cohort

Author

Cristina M. Lanata, Joanne Nititham, Kimberly E. Taylor, Olivia Solomon, Sharon A. Chung, Ashira Blazer, Laura Trupin, Patricia Katz, Maria Dall'Era, Jinoos Yazdany, Marina Sirota, Lisa F. Barcellos, and Lindsey A. Criswell

Subjects
Cross-Sectional Studies, Rheumatology, Immunology, Immunology and Allergy, Humans, Lupus Erythematosus, Systemic, CpG Islands, DNA Methylation, Biomarkers, Immunosuppressive Agents, Epigenesis, Genetic, Genome-Wide Association Study
Abstract

Findings from cross-sectional studies have revealed associations between DNA methylation and systemic lupus erythematosus (SLE) outcomes. This study was undertaken to investigate the dynamics of DNA methylation by examining participants from an SLE longitudinal cohort using samples collected at 2 time points.A total of 101 participants from the California Lupus Epidemiology Study were included in our analysis. DNA was extracted from blood samples collected at the time of enrolment in the cohort and samples collected after 2 years and was analyzed using Illumina EPIC BeadChip kit. Paired t-tests were used to identify genome-wide changes which included 256 CpG sites previously found to be associated with SLE subtypes. Linear mixed models were developed to understand the relationship between DNA methylation and disease activity, medication use, and sample cell-type proportions, adjusted for age, sex, and genetic principal components.The majority of CpGs that were previously determined to be associated with SLE subtypes remained stable over 2 years (185 CpGs [72.3%]; t-test false discovery rate 0.05). Compared to background genome-wide methylation, there was an enrichment of SLE subtype-associated CpGs that changed over time (27.7% versus 0.34%). Changes in cell-type proportions were associated with changes at 67 CpGs (P 2.70 × 10In this longitudinal SLE cohort, we identified a subset of SLE subtype-associated CpGs that remained stable over time and may be useful as biomarkers of disease subtypes. Another subset of SLE subtype-associated CpGs changed at a higher proportion compared to the genome-wide methylome. Additional studies are needed to understand the etiology and impact of these changes on methylation of SLE-associated CpGs.

Published
2022

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

Author

Marjo-Riitta Järvelin, Catherine Allard, Andres Cardenas, Olivia Solomon, Barbara Heude, Vincent W. V. Jaddoe, Wilfried Karmaus, Terence Dwyer, Katri Räikkönen, Darina Czamara, Olena Gruzieva, Isabella Annesi-Maesano, Manolis Kogevinas, Simon Kebede Merid, Hongmei Zhang, Wenche Nystad, Florianne O L Vehmeijer, Erik Melén, Susan Ewart, Lu Gao, Michelle Plusquin, Sarah E. Reese, Munawar Hussain Soomro, Marie-France Hivert, Zdenko Herceg, Andrea A. Baccarelli, Janine F. Felix, Luigi Bouchard, Göran Pershagen, Jordi Sunyer, Alexei Novoloaca, Joseph L. Wiemels, Elisabeth B. Binder, John P. Newnham, Thorkild I. A. Sørensen, Sheryl L. Rifas-Shiman, Ellen A. Nohr, Nabila Kazmi, Carrie V. Breton, Ashok Kumar, Juha Kere, Nina Holland, Josep M. Antó, Debbie A Lawlor, Karen Huen, Rae-Chi Huang, Inger Kull, Brenda Eskenazi, Paolo Vineis, Matthias Wielscher, Monica Cheng Munthe-Kaas, Catarina Almqvist, Cilla Söderhäll, Lucas A. Salas, Jean Bousquet, Alvin T. Kho, Patrice Perron, Petter Brodin, Martine Vrijheid, Kelan G. Tantisira, Per Magnus, Scott T. Weiss, Faisal I. Rezwan, Nour Baïz, Stephanie J. London, Gemma C Sharp, Phillip E. Melton, Emily Oken, Luigi Gagliardi, John W. Holloway, Gerard H. Koppelman, Siri E. Håberg, Caroline L Relton, Leanne K. Küpers, Denise Anderson, Jari Lahti, Tim S. Nawrot, Mariona Bustamante, Priyadarshini Kachroo, S. Hasan Arshad, Dawn L. DeMeo, Liesbeth Duijts, Sylvain Sebert, Shanshan Zhao, Eva Corpeleijn, Judith M. Vonk, Christian M. Page, Harold Snieder, Pooja Jain, Akram Ghantous, Anna Bergström, Cheng-Jian Xu, Ritu Roy, Rezwan, Faisal Ibne/0000-0001-9921-222X, Holloway, John/0000-0001-9998-0464, Lawlor, Debbie A/0000-0002-6793-2262, Salas, Lucas A/0000-0002-2279-4097, Cardenas, Andres/0000-0003-2284-3298, Sharp, Gemma/0000-0003-2906-4035, Lifestyle Medicine (LM), Reproductive Origins of Adult Health and Disease (ROAHD), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Psychology and Logopedics, Developmental Psychology Research Group, Faculty of Medicine, University of Helsinki, STEMM - Stem Cells and Metabolism Research Program, Juha Kere / Principal Investigator, Research Programs Unit, HUS Helsinki and Uusimaa Hospital District, UNIVERSITY OF OULU, Salvy-Córdoba, Nathalie, Karolinska Institutet [Stockholm], Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, International Agency for Cancer Research (IACR), MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni] (MRC IEU), University of Bristol [Bristol], Bristol Medical School, Wageningen University and Research [Wageningen] (WUR), University of Groningen [Groningen], Boston Children's Hospital, Harvard Medical School [Boston] (HMS), University of California [San Francisco] (UC San Francisco), University of California (UC), Helen Diller Family Comprehensive Cancer Center [San Francisco], Southern California University of Health Sciences (SCU), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Imperial College London, Hasselt University (UHasselt), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Faculté de médecine et des sciences de la santé [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Geisel School of Medicine at Dartmouth, Cranfield University, University of Memphis (U of M), University of Oulu, Department of Biology and Biocenter Oulu, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Harvard Pilgrim Health Care Institute, Curtin University [Bentley, WA, Australie], The University of Western Australia (UWA), NIHR Bristol Biomedical Research Centre, Centre for Occupational and Environmental Medicine [Stockholm, Sweden] (Region Stockholm), University of Southern California (USC), University of California [Berkeley] (UC Berkeley), USL Tuscany Northwest, NIHR Health Protection Research Unit, Partenaires INRAE, University Hospitals Leuven [Leuven], University Medical Center Groningen [Groningen] (UMCG), CHUS – Centre Hospitalier Universitaire de Sherbrooke [Sherbrooke, QC, Canada], University of Southern Denmark (SDU), Michigan State University [East Lansing], Michigan State University System, National Institute of Environmental Health Sciences [Durham] (NIEHS-NIH), National Institutes of Health [Bethesda] (NIH), Norwegian Institute of Public Health [Oslo] (NIPH), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Turku Institute for Advanced Studies, Columbia Mailman School of Public Health, Columbia University [New York], Telethon KIDS Institute, Brigham and Women’s Hospital [Boston, MA], Département des Sciences Fondamentales [Saguenay, QC, Canada], Université du Québec à Chicoutimi (UQAC), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), University of Copenhagen = Københavns Universitet (UCPH), University of Southampton, The David Hide Asthma and Allergy Research Centre, St Mary's Hospital-University Hospital Southampton NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust, Nuffield Department of Women's and Reproductive Health (NDWRH), University of Oxford- John Radcliffe Hospital [Oxford University Hospital], Murdoch Children's Research Institute (MCRI), Emory University School of Medicine, Emory University [Atlanta, GA], Brigham and Women's Hospital [Boston], Karolinska Institutet Science Park, Sachs' Children's Hospital, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Research Team on Early life Origins of Health (EarOH), Oslo University Hospital [Oslo], Brigham & Women’s Hospital [Boston] (BWH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Basel (Unibas), Swiss Tropical and Public Health Institute [Basel], Astrid Lindgren Children's Hospital, Karolinska University Hospital [Stockholm], School of Public Health [Berkeley], University of California (UC)-University of California (UC), Beatrix Children's Hospital, Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17165 Sweden., Massachusetts General Hospital [Boston], Erasmus MC other, and Pediatrics

Subjects
Male, Physiology, MESH: Epigenome, Fetal Development, Epigenome, 0302 clinical medicine, MESH: Child, MATERNAL SMOKING, CORD BLOOD, Aetiology, Child, Lung, Genetics & Heredity, 1184 Genetics, developmental biology, physiology, ASSOCIATION, ALSPAC, 3. Good health, Child, Preschool, 030220 oncology & carcinogenesis, Epigenetics, Infant, Premature, Clinical Sciences, Development, 03 medical and health sciences, Clinical Research, Genetics, Humans, Transcriptomics, Premature, Molecular Biology, MESH: Adolescent, 0604 Genetics, Pregnancy, MESH: Humans, Science & Technology, MESH: Child, Preschool, lcsh:R, PRENATAL ARSENIC EXPOSURE, Infant, DNA, DNA Methylation, medicine.disease, 030104 developmental biology, Genetic Loci, COHORT PROFILE, MESH: Female, 0301 basic medicine, MESH: Premature Birth, Nutrition and Disease, lcsh:Medicine, Reproductive health and childbirth, MESH: DNA Methylation, Voeding en Ziekte, 2.1 Biological and endogenous factors, RUNX3 GENE, Genetics (clinical), RISK, Pediatric, MESH: Infant, Newborn, MESH: DNA, Gestational age, Premature birth, Cord blood, DNA methylation, Premature Birth, Molecular Medicine, Female, Life Sciences & Biomedicine, MESH: Fetal Development, MESH: Infant, Premature, lcsh:QH426-470, Adolescent, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: Genetic Loci, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, medicine, Preschool, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Fetus, business.industry, Research, Human Genome, Infant, Newborn, CHILDHOOD ASTHMA, 1103 Clinical Sciences, Preterm birth, Perinatal Period - Conditions Originating in Perinatal Period, Newborn, MESH: Male, lcsh:Genetics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 3111 Biomedicine, WEIGHT, business
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 − 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

Published
2020
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5. Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood

Author

Karen Huen, Robert B. Gunier, Paul Yousefi, Maria Escudero-Fung, Brenda Eskenazi, Nina Holland, Olivia Solomon, and Lisa F. Barcellos

Subjects
0301 basic medicine, medicine.medical_specialty, Pregnancy, education.field_of_study, Epidemiology, Health, Toxicology and Mutagenesis, Population, Phthalate, Physiology, Biology, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Endocrinology, Differentially methylated regions, chemistry, CpG site, Internal medicine, Cord blood, DNA methylation, medicine, Epigenetics, education, Genetics (clinical)
Abstract

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Phthalates are known endocrine disruptors with ubiquitous exposures in the general population including pregnant women, and they have been linked with a number of adverse health outcomes. We examined the association between in utero phthalate exposure and altered patterns of cord blood DNA methylation in 336 Mexican-American newborns. Concentrations of 11 phthalate metabolites were analyzed in maternal urine samples collected at 13 and 26 weeks gestation as a measure of fetal exposure. DNA methylation was assessed using the Infinium HumanMethylation 450K BeadChip adjusting for cord blood cell composition. To identify differentially methylated regions (DMRs) that may be more informative than individual CpG sites, we used two different approaches, DMRcate and comb-p. Regional assessment by both methods identified 27 distinct DMRs, the majority of which were in relation to multiple phthalate metabolites. Most of the significant DMRs (67%) were observed for later pregnancy (26 weeks gestation). Further, 51% of the significant DMRs were associated with the di-(2-ethylhexyl) phthalate metabolites. Five individual CpG sites were associated with phthalate metabolite concentrations after multiple comparisons adjustment (FDR), all showing hypermethylation. Genes with DMRs were involved in inflammatory response (IRAK4 and ESM1), cancer (BRCA1 and LASP1), endocrine function (CNPY1), and male fertility (IFT140, TESC, and PRDM8). These results on differential DNA methylation in newborns with prenatal phthalate exposure provide new insights and targets to explore mechanism of adverse effects of phthalates on human health. Environ. Mol. Mutagen. 58:398-410, 2017. © 2017 Wiley Periodicals, Inc.

Published
2017
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6. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Author

Jenny van Dongen, Anne P. Starling, Patrice Perron, Craig J. Newschaffer, Cheng-Jian Xu, Letizia Trevisi, Lorenzo Richiardi, Todd M. Everson, Alexei Novoloaca, Siri E. Håberg, Allan C. Just, Rolv T. Lie, Denise Anderson, Ivana V. Yang, Lu Gao, Hamdi Mbarek, Susan K. Murphy, Robert O. Wright, Claire Monnereau, Jordi Sunyer, Sophie E. Moore, Gonneke Willemsen, Sylvain Sebert, Gerard H. Koppelman, Andrew P. Feinberg, Andrew M. Prentice, Arnout Standaert, Susan Ewart, Dana Dabelea, Maria C. Magnus, Vilhelmina Ullemar, Matthieu Moisse, Sarah E. Reese, Hongmei Zhang, Pia M. Villa, Philip E. Melton, Samantha Lent, Debbie A Lawlor, Christian M. Page, Harold Snieder, Eva Govarts, H. Marike Boezen, Weiming Zhang, Rosalind J. Wright, Augusto A. Litonjua, Carrie V. Breton, Allen J. Wilcox, Jari Lahti, Jack A. Taylor, Mariona Bustamante, Cathrine Hoyo, Karen Huen, Thorkild I. A. Sørensen, Ellen A. Nohr, Rachel L. Maguire, Lucas A. Salas, Manolis Kogevinas, Ritu Roy, Lawrence J. Beilin, Vincent V. W. Jaddoe, Matthias Wielscher, Carmen J. Marsit, Martine Vrijheid, Emily Oken, Dawn L. DeMeo, Monica Cheng Munthe-Kaas, Judith M. Vonk, Eero Kajantie, Margaret R. Karagas, Joseph L. Wiemels, Zdenko Herceg, Sabine A. S. Langie, Anna Bergström, Brenda Eskenazi, Nina Holland, Akram Ghantous, Catarina Almqvist, Lisa A. Croen, Andrea A. Baccarelli, Michael N. Routledge, Marie-France Hivert, Paul Yousefi, Diana A van der Plaat, Syed Hasan Arshad, Kelly M. Bakulski, Gemma C Sharp, M. Daniele Fallin, Juha Kere, Yun Yun Gong, Marjo-Riitta Järvelin, Catherine Allard, Maaike de Vries, Janine F. Felix, Liesbeth Duijts, Rae-Chi Huang, Joosje H. Heimovaara, Erik Melén, Wilfried Karmaus, Darina Czamara, Katri Räikkönen, Katerina Kechris, Faisal I. Rezwan, Olivia Solomon, Robert Karlsson, Elisabeth B. Binder, Esa Hämäläinen, Leanne K. Küpers, Matt J. Silver, Shanshan Zhao, Eva Corpeleijn, Tim S. Nawrot, Irva Hertz-Picciotto, Stephanie J. London, Simon Kebede Merid, John W. Holloway, Tom G. Richardson, Caroline L Relton, Ulrike Gehring, Luigi Bouchard, Zongli Xu, Anne K. Örtqvist, George Davey Smith, Dereje D. Jima, Wenche Nystad, Dorret I. Boomsma, Michelle Plusquin, Terence Dwyer, Epidemiology, Erasmus MC other, Pediatrics, Groningen Research Institute for Asthma and COPD (GRIAC), Reproductive Origins of Adult Health and Disease (ROAHD), Lifestyle Medicine (LM), Life Course Epidemiology (LCE), Department of Psychology and Logopedics, Helsinki Collegium for Advanced Studies, Faculty of Medicine, University of Helsinki, Department of Obstetrics and Gynecology, Pregnancy and Genes, Clinicum, Medicum, STEMM - Stem Cells and Metabolism Research Program, Juha Kere / Principal Investigator, Research Programs Unit, HUSLAB, Lastentautien yksikkö, Children's Hospital, HUS Gynecology and Obstetrics, HUS Children and Adolescents, Developmental Psychology Research Group, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Methodology, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
Male, 0301 basic medicine, Netherlands Twin Register (NTR), Nutrition and Disease, Epidemiology, Birth Weight/genetics, General Physics and Astronomy, Physiology, 02 engineering and technology, BIOCONDUCTOR, DISEASE, Body Mass Index, Epigenesis, Genetic, Fetal Development, Voeding en Ziekte, Smoking/adverse effects, Birth Weight, Medicine, MATERNAL SMOKING, CORD BLOOD, Child, lcsh:Science, Genome, Multidisciplinary, DNA methylation, Smoking, Confounding, 1184 Genetics, developmental biology, physiology, Methylation, 021001 nanoscience & nanotechnology, 3. Good health, Multidisciplinary Sciences, EPIGENETIC MEDIATION, Folic Acid/blood, PREGNANCY, Adolescent, Adult, CpG Islands, DNA, DNA Methylation, Female, Fetus, Folic Acid, Genome-Wide Association Study, Humans, Infant, Newborn, Pregnancy, Prenatal Exposure Delayed Effects, Genome, Human, MENDELIAN RANDOMIZATION, Science & Technology - Other Topics, Epigenetics, GENETIC-EVIDENCE, epidemiology, 0210 nano-technology, Prenatal Exposure Delayed Effects/blood, FETAL ORIGINS, Human, PACKAGE, Science, Birth weight, DNA/genetics, Paediatric research, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, MD Multidisciplinary, Mendelian randomization, Life Science, Science & Technology, epigenetics, business.industry, Infant, General Chemistry, Epigenome, Newborn, medicine.disease, Fetal Development/genetics, 030104 developmental biology, lcsh:Q, business, Epigenesis
Abstract

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni, Birthweight has been found to associate with later-life health outcomes. Here the authors perform a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, identifying differentially methylated CpGs in neonatal blood that associate with birthweight.

Published
2019
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7. PON1 DNA methylation and neurobehavior in Mexican-American children with prenatal organophosphate exposure

Author

Karen Huen, Katherine Kogut, Brenda Eskenazi, Olivia Solomon, and Nina Holland

Subjects
0301 basic medicine, Male, Genotype, Disease, Bioinformatics, Article, 03 medical and health sciences, Cognition, Memory, Clinical Research, Pregnancy, Mexican Americans, Genetics, medicine, 2.1 Biological and endogenous factors, Humans, Epigenetics, Aetiology, Pesticides, Child, Maternal-Fetal Exchange, lcsh:Environmental sciences, General Environmental Science, Wechsler Intelligence Scale for Children, Pediatric, lcsh:GE1-350, Intelligence quotient, business.industry, Aryldialkylphosphatase, Neurosciences, Infant, Newborn, Infant, Methylation, DNA Methylation, Newborn, medicine.disease, Organophosphates, 030104 developmental biology, Memory, Short-Term, Short-Term, CpG site, IQ, Neurological, DNA methylation, Autism, Female, business, Environmental Sciences
Abstract

PON1 is a multifunctional enzyme involved in oxidative stress and detoxification of some organophosphate (OP) pesticides. It has been associated with nervous system diseases like Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and autism. We previously found that PON1 susceptible genotypes were associated with lower IQ scores in children. Epigenetic marks, such as DNA methylation, can regulate gene expression. Yet, data on whether DNA methylation may influence the relationship between PON1 levels and neurobehavior are limited. In this study, we used Illumina 450K and EPIC BeadChip arrays to assess PON1 DNA methylation in blood specimens collected from children (n = 238) at birth (cord blood) and age 7 years and examined their relationship with cognitive outcomes. The Wechsler Intelligence Scale for Children was used to assess Full Scale IQ and four composite measures (Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed Indexes) in 7-year-old children. We observed a consistent yet nonsignificant inverse relationship of methylation at several CpG sites close to the PON1 transcription start site with Full Scale IQ and other composite measures of cognition. We also found an inverse relationship between cord blood methylation at cg15887283 with working memory and a positive association of 7-year-old methylation at cg22798737 with processing speed, independent of OP exposure. However, none of the associations remained significant after accounting for multiple comparisons. This study provides some evidence of the role DNA methylation may play in the known relationship between PON1 and neurobehavior in children, however it appears to be only suggestive and warrants additional research. Keywords: Epigenetics, Cognition, IQ

Published
2018

8. Genome-wide profiling identifies associations between lupus nephritis and differential methylation of genes regulating tissue hypoxia and type 1 interferon responses

Author

Patrick Coit, Lisa F. Barcellos, Hong L. Quach, Amanda Mok, Joanne Nititham, Olivia Solomon, Renuka R. Nayak, Sharon A. Chung, Lindsey A. Criswell, and Amr H. Sawalha

Subjects
0301 basic medicine, Immunology, Population, Lupus nephritis, Lupus, Biology, Autoimmune Disease, Systemic Lupus Erythematosus, 03 medical and health sciences, Clinical Research, immune system diseases, medicine, Genetics, 2.1 Biological and endogenous factors, Epigenetics, Aetiology, education, skin and connective tissue diseases, Genetic association, education.field_of_study, DNA methylation, Inflammatory and immune system, Human Genome, General Medicine, Methylation, medicine.disease, Lupus Nephritis, 3. Good health, 030104 developmental biology, CpG site, Nephritis
Abstract

Objective Previous studies have shown that differential DNA methylation is associated with SLE susceptibility. How DNA methylation affects the clinical heterogeneity of SLE has not been fully defined. We conducted this study to identify differentially methylated CpG sites associated with nephritis among women with SLE. Methods The methylation status of 428 229 CpG sites across the genome was characterised for peripheral blood cells from 322 women of European descent with SLE, 80 of whom had lupus nephritis, using the Illumina HumanMethylation450 BeadChip. Multivariable linear regression adjusting for population substructure and leucocyte cell proportions was used to identify differentially methylated sites associated with lupus nephritis. The influence of genetic variation on methylation status was investigated using data from a genome-wide association study of SLE. Pathway analyses were used to identify biological processes associated with lupus nephritis. Results We identified differential methylation of 19 sites in 18 genomic regions that was associated with nephritis among patients with SLE (false discovery rate q

Published
2016

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