Clinical Epigenetics (Sep 2023)
Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude
- 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,
- John W. Holloway
Affiliations
- Latha Kadalayil
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton
- Md. Zahangir Alam
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital
- Cory Haley White
- Merck Exploratory Science Center in Cambridge MA, Merck Research Laboratories
- Akram Ghantous
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer
- Esther Walton
- Department of Psychology, University of Bath
- Olena Gruzieva
- Institute of Environmental Medicine, Karolinska Institutet
- Simon Kebede Merid
- Centre for Occupational and Environmental Medicine
- Ashish Kumar
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet
- Ritu P. Roy
- Helen Diller Family Comprehensive Cancer Center University of California
- Olivia Solomon
- Children’s Environmental Health Laboratory, University of California
- Karen Huen
- Children’s Environmental Health Laboratory, University of California
- Brenda Eskenazi
- Children’s Environmental Health Laboratory, University of California
- Peter Rzehak
- Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians Universität München (LMU)
- Veit Grote
- Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians Universität München (LMU)
- Jean-Paul Langhendries
- CHC
- Elvira Verduci
- Department of Pediatrics, Vittore Buzzi Children Hospital, University of Milan
- Natalia Ferre
- Pediatric Nutrition and Human Development Research Unit, Universitat Rovira i Virgili, IISPV
- Darek Gruszfeld
- Neonatal Department, Children’s Memorial Health Institute
- Lu Gao
- Department of Preventive Medicine, University of Southern California
- Weihua Guan
- Division of Biostatistics, School of Public Health, University of Minnesota
- Xuehuo Zeng
- Glotech, Inc.
- Enrique F. Schisterman
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania
- John F. Dou
- Department of Epidemiology, School of Public Health, University of Michigan
- Kelly M. Bakulski
- Department of Epidemiology, School of Public Health, University of Michigan
- Jason I. Feinberg
- Wendy Klag Center for Autism and Developmental Disabilities Johns Hopkins University
- Munawar Hussain Soomro
- Sorbonne Université and INSERM, Epidemiology of Allergic and Respiratory Diseases Department, Pierre Louis Institute of Epidemiology and Public Health (IPLESP UMRS 1136), Saint-Antoine Medical School
- Giancarlo Pesce
- Sorbonne Université and INSERM, Epidemiology of Allergic and Respiratory Diseases Department, Pierre Louis Institute of Epidemiology and Public Health (IPLESP UMRS 1136), Saint-Antoine Medical School
- Nour Baiz
- Institut Desbrest de Santé Publique (IDESP), INSERM and Montpellier University
- Elena Isaevska
- Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin
- Michelle Plusquin
- Center for Environmental Sciences, University of Hasselt
- Marina Vafeiadi
- Department of Social Medicine, School of Medicine, University of Crete
- Theano Roumeliotaki
- Department of Social Medicine, School of Medicine, University of Crete
- Sabine A. S. Langie
- Unit Health, Flemish Institute for Technological Research (VITO)
- Arnout Standaert
- Unit Health, Flemish Institute for Technological Research (VITO)
- Catherine Allard
- Centre de Recherche du Centre Hospitalier de l’Universite de Sherbrooke
- Patrice Perron
- Department of Medicine, Universite de Sherbrooke
- Luigi Bouchard
- Department of Biochemistry and Functional Genomics, Universite de Sherbrooke
- Evelien R. van Meel
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam
- Janine F. Felix
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam
- Vincent W. V. Jaddoe
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam
- Paul D. Yousefi
- Medical Research Council Integrative Epidemiology Unit, University of Bristol
- Cecilia H. Ramlau-Hansen
- Department of Public Health, Aarhus University
- Caroline L. Relton
- Medical Research Council Integrative Epidemiology Unit, University of Bristol
- Elmar W. Tobi
- Periconceptional Epidemiology, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center
- Anne P. Starling
- Life Course Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus
- Ivana V. Yang
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus
- Maria Llambrich
- Institute for Global Health (ISGlobal)
- Gillian Santorelli
- Bradford Institute for Health Research
- Johanna Lepeule
- Institute for Advanced Biosciences, University Grenoble-Alpes, INSERM, CNRS
- Lucas A. Salas
- Institute for Global Health (ISGlobal)
- Mariona Bustamante
- Institute for Global Health (ISGlobal)
- Susan L. Ewart
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University
- Hongmei Zhang
- Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis
- Wilfried Karmaus
- Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis
- Stefan Röder
- Department of Environmental Immunology, Helmholtz Centre for Environmental Research - UFZ
- Ana Claudia Zenclussen
- Department of Environmental Immunology, Helmholtz Centre for Environmental Research - UFZ
- Jianping Jin
- 2530 Meridian Pkwy, Suite 200
- Wenche Nystad
- Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health
- Christian M. Page
- Centre for Fertility and Health, Norwegian Institute of Public Health
- Maria Magnus
- Centre for Fertility and Health, Norwegian Institute of Public Health
- Dereje D. Jima
- Center for Human Health and the Environment, North Carolina State University
- Cathrine Hoyo
- Center for Human Health and the Environment, North Carolina State University
- Rachel L. Maguire
- Department of Biological Sciences, North Carolina State University
- Tuomas Kvist
- Department of Psychology and Logopedics, University of Helsinki
- Darina Czamara
- Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry
- Katri Räikkönen
- Department of Psychology and Logopedics, University of Helsinki
- Tong Gong
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Vilhelmina Ullemar
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Sheryl L. Rifas-Shiman
- Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute
- Emily Oken
- Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute
- Catarina Almqvist
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Robert Karlsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Jari Lahti
- Department of Psychology and Logopedics, University of Helsinki
- Susan K. Murphy
- Department of Obstetrics and Gynaecology, Duke University Medical Center
- Siri E. Håberg
- Centre for Fertility and Health, Norwegian Institute of Public Health
- Stephanie London
- Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health
- Gunda Herberth
- Department of Environmental Immunology, Helmholtz Centre for Environmental Research - UFZ
- Hasan Arshad
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton
- Jordi Sunyer
- Institute for Global Health (ISGlobal)
- Regina Grazuleviciene
- Department of Environmental Science, Vytautas Magnus University
- Dana Dabelea
- Life Course Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus
- Régine P. M. Steegers-Theunissen
- Periconceptional Epidemiology, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center
- Ellen A. Nohr
- Department of Clinical Research, Odense Universitetshospital
- Thorkild I. A. Sørensen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
- Liesbeth Duijts
- The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam
- Marie-France Hivert
- Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute
- Vera Nelen
- Provincial Institute for Hygiene
- Maja Popovic
- Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin
- Manolis Kogevinas
- Institute for Global Health (ISGlobal)
- Tim S. Nawrot
- Center for Environmental Sciences, University of Hasselt
- Zdenko Herceg
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer
- Isabella Annesi-Maesano
- Institut Desbrest de Santé Publique (IDESP), INSERM and Montpellier University
- M. Daniele Fallin
- Wendy Klag Center for Autism and Developmental Disabilities Johns Hopkins University
- Edwina Yeung
- Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Carrie V. Breton
- Department of Preventive Medicine, University of Southern California
- Berthold Koletzko
- Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians Universität München (LMU)
- Nina Holland
- Children’s Environmental Health Laboratory, CERCH, Berkeley Public Health, University of California
- Joseph L. Wiemels
- Center for Genetic Epidemiology, University of Southern California
- Erik Melén
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet
- Gemma C. Sharp
- Medical Research Council Integrative Epidemiology Unit, University of Bristol
- Matt J. Silver
- Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine
- Faisal I. Rezwan
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital
- John W. Holloway
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital
- DOI
- https://doi.org/10.1186/s13148-023-01542-5
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 23
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 < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N). Conclusions In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes.
Keywords
