Meta-Analysis

. 2023 Sep 11;15(1):148.

doi: 10.1186/s13148-023-01542-5.

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

Latha Kadalayil^{1

2}, Md Zahangir Alam^{2

3}, Cory Haley White⁴, Akram Ghantous⁵, Esther Walton^#⁶, Olena Gruzieva^{7

8}, Simon Kebede Merid⁸, Ashish Kumar⁹, Ritu P Roy^{10

11}, Olivia Solomon¹², Karen Huen¹², Brenda Eskenazi¹², Peter Rzehak¹³, Veit Grote¹³, Jean-Paul Langhendries¹⁴, Elvira Verduci¹⁵, Natalia Ferre¹⁶, Darek Gruszfeld¹⁷, Lu Gao¹⁸, Weihua Guan¹⁹, Xuehuo Zeng²⁰, Enrique F Schisterman²¹, John F Dou²², Kelly M Bakulski²², Jason I Feinberg^{23

24}, Munawar Hussain Soomro^{25

26}, Giancarlo Pesce²⁵, Nour Baiz²⁷, Elena Isaevska²⁸, Michelle Plusquin²⁹, Marina Vafeiadi³⁰, Theano Roumeliotaki³⁰, Sabine A S Langie^{31

32

33}, Arnout Standaert³¹, Catherine Allard³⁴, Patrice Perron³⁵, Luigi Bouchard^{36

37}, Evelien R van Meel^{38

39}, Janine F Felix^{38

40}, Vincent W V Jaddoe^{38

40}, Paul D Yousefi^{41

42}, Cecilia H Ramlau-Hansen⁴³, Caroline L Relton^{41

42}, Elmar W Tobi⁴⁴, Anne P Starling^{45

46

47}, Ivana V Yang^{46

48

49}, Maria Llambrich^{50

51

52}, Gillian Santorelli⁵³, Johanna Lepeule⁵⁴, Lucas A Salas^{50

55

56

57}, Mariona Bustamante^{50

51

52}, Susan L Ewart⁵⁸, Hongmei Zhang⁵⁹, Wilfried Karmaus⁵⁹, Stefan Röder⁶⁰, Ana Claudia Zenclussen⁶⁰, Jianping Jin⁶¹, Wenche Nystad⁶², Christian M Page^{63

64}, Maria Magnus⁶³, Dereje D Jima^{65

66}, Cathrine Hoyo^{65

67}, Rachel L Maguire^{67

68}, Tuomas Kvist⁶⁹, Darina Czamara⁷⁰, Katri Räikkönen⁶⁹, Tong Gong⁷¹, Vilhelmina Ullemar⁷¹, Sheryl L Rifas-Shiman⁷², Emily Oken^#⁷², Catarina Almqvist^#^{71

73}, Robert Karlsson⁷¹, Jari Lahti⁶⁹, Susan K Murphy⁶⁸, Siri E Håberg⁶³, Stephanie London⁷⁴, Gunda Herberth⁶⁰, Hasan Arshad^{1

75

76}, Jordi Sunyer^{50

51

52}, Regina Grazuleviciene⁷⁷, Dana Dabelea^{45

46

78}, Régine P M Steegers-Theunissen⁴⁴, Ellen A Nohr⁷⁹, Thorkild I A Sørensen^{80

81}, Liesbeth Duijts^{38

39

82}, Marie-France Hivert^{72

83}, Vera Nelen⁸⁴, Maja Popovic²⁸, Manolis Kogevinas⁵⁰, Tim S Nawrot^{29

85}, Zdenko Herceg⁵, Isabella Annesi-Maesano²⁷, M Daniele Fallin^{23

24}, Edwina Yeung⁸⁶, Carrie V Breton¹⁸, Berthold Koletzko¹³, Nina Holland⁸⁷, Joseph L Wiemels^{88

89}, Erik Melén^{9

90}, Gemma C Sharp^{41

91}, Matt J Silver^{92

93}, Faisal I Rezwan^#^{2

94}, John W Holloway^#^{95

96}

Affiliations

¹ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
² Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
³ Department of Computer Science and Engineering, Bangladesh University of Engineering and Technology, Dhaka, Bangladesh.
⁴ Merck Exploratory Science Center in Cambridge MA, Merck Research Laboratories, Cambridge, MA, 02141, USA.
⁵ Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France.
⁶ Department of Psychology, University of Bath, Bath, UK.
⁷ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁸ Centre for Occupational and Environmental Medicine, Region Stockholm, Sweden.
⁹ Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Helen Diller Family Comprehensive Cancer Center University of California, San Francisco, CA, 94143, USA.
¹¹ Computational Biology and Informatics Core, University of California, San Francisco, CA, 94143, USA.
¹² Children's Environmental Health Laboratory, University of California, Berkeley, CA, USA.
¹³ Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians Universität München (LMU), Munich, Germany.
¹⁴ CHC, St Vincent, Liège-Rocourt, Belgium.
¹⁵ Department of Pediatrics, Vittore Buzzi Children Hospital, University of Milan, Milan, Italy.
¹⁶ Pediatric Nutrition and Human Development Research Unit, Universitat Rovira i Virgili, IISPV, Reus, Spain.
¹⁷ Neonatal Department, Children's Memorial Health Institute, Warsaw, Poland.
¹⁸ Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁹ Division of Biostatistics, School of Public Health, University of Minnesota, A460 Mayo Building, MMC 303, 420 Delaware St. SE, Minneapolis, MN, 55455, USA.
²⁰ Glotech, Inc., Rockville, MD, USA.
²¹ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA, 19104, USA.
²² Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
²³ Wendy Klag Center for Autism and Developmental Disabilities Johns Hopkins University, Baltimore, MD, USA.
²⁴ Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
²⁵ 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, Paris Cedex 12, France.
²⁶ Department of Community Medicine and Public Health, SMBB Medical University, Larkana, Pakistan.
²⁷ Institut Desbrest de Santé Publique (IDESP), INSERM and Montpellier University, Montpellier, France.
²⁸ Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, CPO Piemonte, Italy.
²⁹ Center for Environmental Sciences, University of Hasselt, 3590, Diepenbeek, Belgium.
³⁰ Department of Social Medicine, School of Medicine, University of Crete, Heraklion, Greece.
³¹ Unit Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
³² Faculty of Sciences, Hasselt University, Diepenbeek, Belgium.
³³ Department of Pharmacology and Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Limburg, The Netherlands.
³⁴ Centre de Recherche du Centre Hospitalier de l'Universite de Sherbrooke, Sherbrooke, Canada.
³⁵ Department of Medicine, Universite de Sherbrooke, Sherbrooke, Canada.
³⁶ Department of Biochemistry and Functional Genomics, Universite de Sherbrooke, Sherbrooke, Canada.
³⁷ Clinical Department of Laboratory Medicine, Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Chicoutimi, Canada.
³⁸ The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
³⁹ Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴⁰ Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴¹ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁴² Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
⁴³ Department of Public Health, Aarhus University, Aarhus, Denmark.
⁴⁴ Periconceptional Epidemiology, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
⁴⁵ Life Course Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴⁶ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴⁷ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁸ Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴⁹ Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA.
⁵⁰ Institute for Global Health (ISGlobal), Barcelona, Spain.
⁵¹ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
⁵² CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
⁵³ Bradford Institute for Health Research, Bradford, UK.
⁵⁴ Institute for Advanced Biosciences, University Grenoble-Alpes, INSERM, CNRS, Grenoble, France.
⁵⁵ Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA.
⁵⁶ Center for Molecular Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA.
⁵⁷ Children's Environmental Health and Disease Prevention Research Center at Dartmouth, Lebanon, NH, USA.
⁵⁸ Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
⁵⁹ Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, USA.
⁶⁰ Department of Environmental Immunology, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany.
⁶¹ 2530 Meridian Pkwy, Suite 200, Durham, NC 27713, USA.
⁶² Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway.
⁶³ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
⁶⁴ Section for Statistics and Data Science, Department of Mathematics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
⁶⁵ Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
⁶⁶ Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA.
⁶⁷ Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
⁶⁸ Department of Obstetrics and Gynaecology, Duke University Medical Center, Durham, NC, USA.
⁶⁹ Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
⁷⁰ Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804, Munich, Germany.
⁷¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷² Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, USA.
⁷³ Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
⁷⁴ Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, RTP, NC, 27709, USA.
⁷⁵ David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.
⁷⁶ NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Southampton, UK.
⁷⁷ Department of Environmental Science, Vytautas Magnus University, 44248, Kaunas, Lithuania.
⁷⁸ Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁷⁹ Department of Clinical Research, Odense Universitetshospital, Odense, Denmark.
⁸⁰ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁸¹ Department Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁸² Division of Neonatology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁸³ Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
⁸⁴ Provincial Institute for Hygiene, Antwerp, Belgium.
⁸⁵ Department of Public Health and Primary Care, Leuven University, Louvain, Belgium.
⁸⁶ Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Dr, MSC 7004, Bethesda, MD, USA.
⁸⁷ Children's Environmental Health Laboratory, CERCH, Berkeley Public Health, University of California, 2121 Berkeley Way #5216, Berkeley, CA, 94720, USA.
⁸⁸ Center for Genetic Epidemiology, University of Southern California, Los Angeles, CA, 90033, USA.
⁸⁹ Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA.
⁹⁰ Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
⁹¹ School of Psychology, University of Exeter, Exeter, UK.
⁹² Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
⁹³ Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, London, UK.
⁹⁴ Department of Computer Science, Aberystwyth University, Aberystwyth, Ceredigion, UK.
⁹⁵ Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK. J.W.Holloway@soton.ac.uk.
⁹⁶ NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Southampton, UK. J.W.Holloway@soton.ac.uk.

^# Contributed equally.

PMID: 37697338
PMCID: PMC10496224
DOI: 10.1186/s13148-023-01542-5

Meta-Analysis

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

Latha Kadalayil et al. Clin Epigenetics. 2023.

. 2023 Sep 11;15(1):148.

doi: 10.1186/s13148-023-01542-5.

Authors

Affiliations

¹ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
² Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
³ Department of Computer Science and Engineering, Bangladesh University of Engineering and Technology, Dhaka, Bangladesh.
⁴ Merck Exploratory Science Center in Cambridge MA, Merck Research Laboratories, Cambridge, MA, 02141, USA.
⁵ Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France.
⁶ Department of Psychology, University of Bath, Bath, UK.
⁷ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁸ Centre for Occupational and Environmental Medicine, Region Stockholm, Sweden.
⁹ Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Helen Diller Family Comprehensive Cancer Center University of California, San Francisco, CA, 94143, USA.
¹¹ Computational Biology and Informatics Core, University of California, San Francisco, CA, 94143, USA.
¹² Children's Environmental Health Laboratory, University of California, Berkeley, CA, USA.
¹³ Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians Universität München (LMU), Munich, Germany.
¹⁴ CHC, St Vincent, Liège-Rocourt, Belgium.
¹⁵ Department of Pediatrics, Vittore Buzzi Children Hospital, University of Milan, Milan, Italy.
¹⁶ Pediatric Nutrition and Human Development Research Unit, Universitat Rovira i Virgili, IISPV, Reus, Spain.
¹⁷ Neonatal Department, Children's Memorial Health Institute, Warsaw, Poland.
¹⁸ Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁹ Division of Biostatistics, School of Public Health, University of Minnesota, A460 Mayo Building, MMC 303, 420 Delaware St. SE, Minneapolis, MN, 55455, USA.
²⁰ Glotech, Inc., Rockville, MD, USA.
²¹ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA, 19104, USA.
²² Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
²³ Wendy Klag Center for Autism and Developmental Disabilities Johns Hopkins University, Baltimore, MD, USA.
²⁴ Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
²⁵ 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, Paris Cedex 12, France.
²⁶ Department of Community Medicine and Public Health, SMBB Medical University, Larkana, Pakistan.
²⁷ Institut Desbrest de Santé Publique (IDESP), INSERM and Montpellier University, Montpellier, France.
²⁸ Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, CPO Piemonte, Italy.
²⁹ Center for Environmental Sciences, University of Hasselt, 3590, Diepenbeek, Belgium.
³⁰ Department of Social Medicine, School of Medicine, University of Crete, Heraklion, Greece.
³¹ Unit Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
³² Faculty of Sciences, Hasselt University, Diepenbeek, Belgium.
³³ Department of Pharmacology and Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Limburg, The Netherlands.
³⁴ Centre de Recherche du Centre Hospitalier de l'Universite de Sherbrooke, Sherbrooke, Canada.
³⁵ Department of Medicine, Universite de Sherbrooke, Sherbrooke, Canada.
³⁶ Department of Biochemistry and Functional Genomics, Universite de Sherbrooke, Sherbrooke, Canada.
³⁷ Clinical Department of Laboratory Medicine, Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Chicoutimi, Canada.
³⁸ The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
³⁹ Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴⁰ Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴¹ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁴² Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
⁴³ Department of Public Health, Aarhus University, Aarhus, Denmark.
⁴⁴ Periconceptional Epidemiology, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
⁴⁵ Life Course Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴⁶ Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴⁷ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁸ Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴⁹ Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA.
⁵⁰ Institute for Global Health (ISGlobal), Barcelona, Spain.
⁵¹ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
⁵² CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
⁵³ Bradford Institute for Health Research, Bradford, UK.
⁵⁴ Institute for Advanced Biosciences, University Grenoble-Alpes, INSERM, CNRS, Grenoble, France.
⁵⁵ Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA.
⁵⁶ Center for Molecular Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA.
⁵⁷ Children's Environmental Health and Disease Prevention Research Center at Dartmouth, Lebanon, NH, USA.
⁵⁸ Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
⁵⁹ Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, USA.
⁶⁰ Department of Environmental Immunology, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany.
⁶¹ 2530 Meridian Pkwy, Suite 200, Durham, NC 27713, USA.
⁶² Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway.
⁶³ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
⁶⁴ Section for Statistics and Data Science, Department of Mathematics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
⁶⁵ Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
⁶⁶ Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA.
⁶⁷ Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
⁶⁸ Department of Obstetrics and Gynaecology, Duke University Medical Center, Durham, NC, USA.
⁶⁹ Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
⁷⁰ Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, 80804, Munich, Germany.
⁷¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷² Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, USA.
⁷³ Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
⁷⁴ Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, RTP, NC, 27709, USA.
⁷⁵ David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.
⁷⁶ NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Southampton, UK.
⁷⁷ Department of Environmental Science, Vytautas Magnus University, 44248, Kaunas, Lithuania.
⁷⁸ Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁷⁹ Department of Clinical Research, Odense Universitetshospital, Odense, Denmark.
⁸⁰ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁸¹ Department Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁸² Division of Neonatology, Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁸³ Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
⁸⁴ Provincial Institute for Hygiene, Antwerp, Belgium.
⁸⁵ Department of Public Health and Primary Care, Leuven University, Louvain, Belgium.
⁸⁶ Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Dr, MSC 7004, Bethesda, MD, USA.
⁸⁷ Children's Environmental Health Laboratory, CERCH, Berkeley Public Health, University of California, 2121 Berkeley Way #5216, Berkeley, CA, 94720, USA.
⁸⁸ Center for Genetic Epidemiology, University of Southern California, Los Angeles, CA, 90033, USA.
⁸⁹ Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA.
⁹⁰ Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
⁹¹ School of Psychology, University of Exeter, Exeter, UK.
⁹² Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
⁹³ Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, London, UK.
⁹⁴ Department of Computer Science, Aberystwyth University, Aberystwyth, Ceredigion, UK.
⁹⁵ Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK. J.W.Holloway@soton.ac.uk.
⁹⁶ NIHR Southampton Biomedical Research Centre, Southampton General Hospital, Southampton, UK. J.W.Holloway@soton.ac.uk.

^# Contributed equally.

PMID: 37697338
PMCID: PMC10496224
DOI: 10.1186/s13148-023-01542-5

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: Birth season; DNA methylation; Differentially methylated regions (DMR); Latitude; Meta-analysis; PACE.

PubMed Disclaimer

Conflict of interest statement

None declared any competing interests.

Figures

**Fig. 1**
Schematic diagram for the season of birth-DNA methylation (DNAm) analyses. Numbers included in the analyses are indicated. *PACE* Pregnancy And Childhood Epigenetics, *EWAS* Epigenome Wide Association Study, *DMP* Differentially Methylated Probe, *FDR* False Positive Rate, *DMR* Differentially Methylated Region. EWASs and meta-analysis were carried out on at-birth and childhood samples separately. All participating cohorts were from the northern hemisphere (range 37.2–71.2°N). Latitude ≥ 50°N represents a subset of cohorts from 50 to 71.2°N (referred to as “higher latitude subgroup” in the text). Latitude < 50°N is a subset of cohorts from 32.7 to 50°N (referred to as “lower latitude subgroup” in the text. ^a27 independent cohorts, but a total of 33 datasets as 6 cohorts contributed to both at-birth and childhood analyses. ^bAt-birth blood samples (cord and heel prick). ^cWhole blood samples (age 1–11 years). ^dThis analysis was not done due to its small sample size

**Fig. 2**
Manhattan plots of the meta-analysed data showing the association of season of birth and DNA methylation at birth using neonatal blood data (A) and during childhood using whole blood data (B). Birth seasons with FDR-significant CpGs when compared to autumn as the reference season alone are shown in the figure. The blue and red lines indicate the threshold p values for false discovery rate (FDR) and the Bonferroni adjustments, respectively. The observed p values on the Y-axis are from models adjusted for covariates and cell types for the seasons indicated in the figures when compared to autumn as the reference season. Genes associated with the CpGs (circled) are indicated. All cohort-specific EWAS analyses were adjusted for gender of the child, gestational age at delivery, maternal age at delivery, maternal smoking during pregnancy, maternal socio-economic status, batch, child’s age at the time of sample collection (in the case of childhood samples and if data were available) and estimated cell proportions. *This CpG (cg01801443, location: intergenic) has a SNP within 10 base pairs and is not included in Table 1

**Fig. 3**
Quantile–quantile (Q-Q) plots for post-meta-analysis models for association between seasons of birth and DNA methylation (primary analyses) for at-birth (A and B) and childhood (C and D) samples. The Q–Q plots were generated by plotting observed p values (y-axis) against the expected uniform distribution of p values under the null hypothesis of no association (x-axis). Lambda and bias were estimated using BACON method [37]. All cohort-specific EWAS analyses were adjusted for gender of the child, gestational age at delivery, maternal age at delivery, maternal smoking during pregnancy, maternal socio-economic status, batch, child’s age at the time of sample collection and estimated cell proportions

See this image and copyright information in PMC

References

1. Weber GW, Prossinger H, Seidler H. Height depends on month of birth. Nature. 1998;391(6669):754–755. - PubMed
1. Brennan PJ, Greenberg G, Miall WE, Thompson SG. Seasonal variation in arterial blood pressure. Br Med J Clin Res Ed. 1982;285(6346):919–923. - PMC - PubMed
1. Gordon DJ, Trost DC, Hyde J, et al. Seasonal cholesterol cycles: the Lipid Research Clinics Coronary Primary Prevention Trial placebo group. Circulation. 1987;76(6):1224–1231. - PubMed
1. Foster RG, Roenneberg T. Human responses to the geophysical daily, annual and lunar cycles. Curr Biol. 2008;18(17):R784–R794. - PubMed
1. Doblhammer G, Vaupel JW. Lifespan depends on month of birth. Proc Natl Acad Sci USA. 2001;98(5):2934–2939. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous