Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude.
Journal: Clinical epigenetics
Volume: 15
Issue: 1
Year of Publication: 2023
Affiliated Institutions:
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
Merck Exploratory Science Center in Cambridge MA, Merck Research Laboratories, Cambridge, MA, , USA.
Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France.
Department of Psychology, University of Bath, Bath, UK.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Centre for Occupational and Environmental Medicine, Region Stockholm, Sweden.
Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Helen Diller Family Comprehensive Cancer Center University of California, San Francisco, CA, , USA.
Children's Environmental Health Laboratory, University of California, Berkeley, CA, USA.
Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians Universität München (LMU), Munich, Germany.
CHC, St Vincent, Liège-Rocourt, Belgium.
Department of Pediatrics, Vittore Buzzi Children Hospital, University of Milan, Milan, Italy.
Pediatric Nutrition and Human Development Research Unit, Universitat Rovira i Virgili, IISPV, Reus, Spain.
Neonatal Department, Children's Memorial Health Institute, Warsaw, Poland.
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
Division of Biostatistics, School of Public Health, University of Minnesota, A Mayo Building, MMC , Delaware St. SE, Minneapolis, MN, , USA.
Glotech, Inc., Rockville, MD, USA.
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Guardian Drive, Philadelphia, PA, , USA.
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA.
Wendy Klag Center for Autism and Developmental Disabilities Johns Hopkins University, Baltimore, MD, USA.
Sorbonne Université and INSERM, Epidemiology of Allergic and Respiratory Diseases Department, Pierre Louis Institute of Epidemiology and Public Health (IPLESP UMRS ), Saint-Antoine Medical School, Paris Cedex , France.
Institut Desbrest de Santé Publique (IDESP), INSERM and Montpellier University, Montpellier, France.
Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, CPO Piemonte, Italy.
Center for Environmental Sciences, University of Hasselt, , Diepenbeek, Belgium.
Department of Social Medicine, School of Medicine, University of Crete, Heraklion, Greece.
Unit Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
Centre de Recherche du Centre Hospitalier de l'Universite de Sherbrooke, Sherbrooke, Canada.
Department of Medicine, Universite de Sherbrooke, Sherbrooke, Canada.
Department of Biochemistry and Functional Genomics, Universite de Sherbrooke, Sherbrooke, Canada.
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Department of Public Health, Aarhus University, Aarhus, Denmark.
Periconceptional Epidemiology, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, PO Box , CA, Rotterdam, The Netherlands.
Life Course Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Institute for Global Health (ISGlobal), Barcelona, Spain.
Bradford Institute for Health Research, Bradford, UK.
Institute for Advanced Biosciences, University Grenoble-Alpes, INSERM, CNRS, Grenoble, France.
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.
Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, USA.
Department of Environmental Immunology, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany.
Meridian Pkwy, Suite , Durham, NC , USA.
Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway.
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, , Munich, Germany.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, USA.
Department of Obstetrics and Gynaecology, Duke University Medical Center, Durham, NC, USA.
Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, RTP, NC, , USA.
Department of Environmental Science, Vytautas Magnus University, , Kaunas, Lithuania.
Department of Clinical Research, Odense Universitetshospital, Odense, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Provincial Institute for Hygiene, Antwerp, Belgium.
Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, B Rockledge Dr, MSC , Bethesda, MD, USA.
Children's Environmental Health Laboratory, CERCH, Berkeley Public Health, University of California, Berkeley Way #, Berkeley, CA, , USA.
Center for Genetic Epidemiology, University of Southern California, Los Angeles, CA, , USA.
Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK. J.W.Holloway@soton.ac.uk.
Abstract summary
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.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.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).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.
Authors & Co-authors:
Kadalayil Latha L
Alam Md Zahangir MZ
White Cory Haley CH
Ghantous Akram A
Walton Esther E
Gruzieva Olena O
Merid Simon Kebede SK
Kumar Ashish A
Roy Ritu P RP
Solomon Olivia O
Huen Karen K
Eskenazi Brenda B
Rzehak Peter P
Grote Veit V
Langhendries Jean-Paul JP
Verduci Elvira E
Ferre Natalia N
Gruszfeld Darek D
Gao Lu L
Guan Weihua W
Zeng Xuehuo X
Schisterman Enrique F EF
Dou John F JF
Bakulski Kelly M KM
Feinberg Jason I JI
Soomro Munawar Hussain MH
Pesce Giancarlo G
Baiz Nour N
Isaevska Elena E
Plusquin Michelle M
Vafeiadi Marina M
Roumeliotaki Theano T
Langie Sabine A S SAS
Standaert Arnout A
Allard Catherine C
Perron Patrice P
Bouchard Luigi L
van Meel Evelien R ER
Felix Janine F JF
Jaddoe Vincent W V VWV
Yousefi Paul D PD
Ramlau-Hansen Cecilia H CH
Relton Caroline L CL
Tobi Elmar W EW
Starling Anne P AP
Yang Ivana V IV
Llambrich Maria M
Santorelli Gillian G
Lepeule Johanna J
Salas Lucas A LA
Bustamante Mariona M
Ewart Susan L SL
Zhang Hongmei H
Karmaus Wilfried W
Röder Stefan S
Zenclussen Ana Claudia AC
Jin Jianping J
Nystad Wenche W
Page Christian M CM
Magnus Maria M
Jima Dereje D DD
Hoyo Cathrine C
Maguire Rachel L RL
Kvist Tuomas T
Czamara Darina D
Räikkönen Katri K
Gong Tong T
Ullemar Vilhelmina V
Rifas-Shiman Sheryl L SL
Oken Emily E
Almqvist Catarina C
Karlsson Robert R
Lahti Jari J
Murphy Susan K SK
Håberg Siri E SE
London Stephanie S
Herberth Gunda G
Arshad Hasan H
Sunyer Jordi J
Grazuleviciene Regina R
Dabelea Dana D
Steegers-Theunissen Régine P M RPM
Nohr Ellen A EA
Sørensen Thorkild I A TIA
Duijts Liesbeth L
Hivert Marie-France MF
Nelen Vera V
Popovic Maja M
Kogevinas Manolis M
Nawrot Tim S TS
Herceg Zdenko Z
Annesi-Maesano Isabella I
Fallin M Daniele MD
Yeung Edwina E
Breton Carrie V CV
Koletzko Berthold B
Holland Nina N
Wiemels Joseph L JL
Melén Erik E
Sharp Gemma C GC
Silver Matt J MJ
Rezwan Faisal I FI
Holloway John W JW
Study Outcome
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