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


Journal

Genome medicine
ISSN: 1756-994X
Titre abrégé: Genome Med
Pays: England
ID NLM: 101475844

Informations de publication

Date de publication:
25 11 2020
Historique:
received: 29 03 2020
accepted: 12 11 2020
entrez: 26 11 2020
pubmed: 27 11 2020
medline: 6 11 2021
Statut: epublish

Résumé

DNA 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. We 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. DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10 There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

Sections du résumé

BACKGROUND
DNA 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.
METHODS
We 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.
RESULTS
DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10
CONCLUSIONS
There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

Identifiants

pubmed: 33239103
doi: 10.1186/s13073-020-00810-w
pii: 10.1186/s13073-020-00810-w
pmc: PMC7687793
doi:

Types de publication

Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

105

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK076648
Pays : United States
Organisme : NIEHS NIH HHS
ID : R24 ES028529
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES014947
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : R01 HD068437
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK085173
Pays : United States
Organisme : NIEHS NIH HHS
ID : R24 ES028531
Pays : United States
Organisme : Medical Research Council
ID : MR/S036520/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : NIEHS NIH HHS
ID : R00 ES025817
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES022934
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM104416
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK048520
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12013/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S03658X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S009310/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S019669/1
Pays : United Kingdom

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Auteurs

Florianne O L Vehmeijer (FOL)

The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Room Na-2918, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, the Netherlands.
Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Leanne K Küpers (LK)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.

Gemma C Sharp (GC)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Lucas A Salas (LA)

Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
ISGlobal, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Samantha Lent (S)

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

Dereje D Jima (DD)

Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA.
Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.

Gwen Tindula (G)

Children's Environmental Health Laboratory, Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.

Sarah Reese (S)

Department of Health and Human Services, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.

Cancan Qi (C)

University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, Groningen, The Netherlands.
University Medical Center Groningen GRIAC Research Institute, University of Groningen, Groningen, the Netherlands.

Olena Gruzieva (O)

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden.

Christian Page (C)

Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.

Faisal I Rezwan (FI)

School of Water, Energy and Environment, Cranfield University, Cranfield, Bedfordshire, UK.
Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.

Philip E Melton (PE)

School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, Western Australia, Australia.
School of Biomedical Sciences, The University of Western Australia, Crawley, Western Austalia, Australia.

Ellen Nohr (E)

Centre for Women's, Family and Child Health, University of South-Eastern Norway, Kongsberg, Norway.
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.

Geòrgia Escaramís (G)

CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
Research group on Statistics, Econometrics and Health (GRECS), University of Girona, Girona, Spain.

Peter Rzehak (P)

Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians Universität München (LMU), Munich, Germany.

Anni Heiskala (A)

Center for Life Course Health Research, University of Oulu, Oulu, Finland.

Tong Gong (T)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Samuli T Tuominen (ST)

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Lu Gao (L)

Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.

Jason P Ross (JP)

CSIRO Health and Biosecurity, North Ryde, New South Wales, Australia.

Anne P Starling (AP)

Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

John W Holloway (JW)

Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

Paul Yousefi (P)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Gunn Marit Aasvang (GM)

Department of Air Pollution and Noise, Norwegian Institute of Public Health, Oslo, Norway.

Lawrence J Beilin (LJ)

Medical School, University of Western Australia, Perth, Australia.

Anna Bergström (A)

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden.

Elisabeth Binder (E)

Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, Munich, Germany.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.

Leda Chatzi (L)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Eva Corpeleijn (E)

University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.

Darina Czamara (D)

Department of Translational Research in Psychiatry, Max-Planck-Institute of Psychiatry, Munich, Germany.

Brenda Eskenazi (B)

Center for Environmental Research and Children's Health, School of Public Health, University of California, Berkeley, CA, USA.

Susan Ewart (S)

College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA.

Natalia Ferre (N)

Pediatrics, Nutrition and Development Research Unit, Universitat Rovira i Virgili, IISPV, Reus, Spain.

Veit Grote (V)

Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians Universität München (LMU), Munich, Germany.

Dariusz Gruszfeld (D)

Neonatal Department, Children's Memorial Health Institute, Warsaw, Poland.

Siri E Håberg (SE)

Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.

Cathrine Hoyo (C)

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.

Karen Huen (K)

Children's Environmental Health Laboratory, Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.

Robert Karlsson (R)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Inger Kull (I)

Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.

Jean-Paul Langhendries (JP)

CHC, St Vincent, Liège-Rocourt, Belgium.

Johanna Lepeule (J)

Université Grenoble Alpes, Inserm, CNRS, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, IAB, Grenoble, France.

Maria C Magnus (MC)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.

Rachel L Maguire (RL)

Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
Department of Obstetrics and Gynecology, Duke University Medical Center, Raleigh, NC, USA.

Peter L Molloy (PL)

CSIRO Health and Biosecurity, North Ryde, New South Wales, Australia.

Claire Monnereau (C)

The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Room Na-2918, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Trevor A Mori (TA)

Medical School, University of Western Australia, Perth, Australia.

Emily Oken (E)

Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Katri Räikkönen (K)

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Sheryl Rifas-Shiman (S)

Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Carlos Ruiz-Arenas (C)

ISGlobal, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Sylvain Sebert (S)

Center for Life Course Health Research, University of Oulu, Oulu, Finland.

Vilhelmina Ullemar (V)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Elvira Verduci (E)

Department of Pediatrics, San Paolo Hospital, University of Milan, Milan, Italy.

Judith M Vonk (JM)

University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.
University Medical Center Groningen GRIAC Research Institute, University of Groningen, Groningen, the Netherlands.

Cheng-Jian Xu (CJ)

University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, Groningen, The Netherlands.
University Medical Center Groningen GRIAC Research Institute, University of Groningen, Groningen, the Netherlands.
Department of Gastroenterology, Hepatology and Endocrinology, CiiM, Centre for Individualised Infection Medicine, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.

Ivana V Yang (IV)

Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Center for Genes, Environment and Health, National Jewish Health, Denver, CO, USA.

Hongmei Zhang (H)

Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis, Memphis, TN, USA.

Weiming Zhang (W)

Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA.

Wilfried Karmaus (W)

Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis, Memphis, TN, USA.

Dana Dabelea (D)

Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Beverly S Muhlhausler (BS)

CSIRO Health and Biosecurity, Adelaide, SA, Australia.

Carrie V Breton (CV)

Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.

Jari Lahti (J)

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Turku Institute for Advanced Studies, University of Turku, Turku, Finland.

Catarina Almqvist (C)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.

Marjo-Riitta Jarvelin (MR)

Center for Life Course Health Research, University of Oulu, Oulu, Finland.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland.
Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK.

Berthold Koletzko (B)

Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians Universität München (LMU), Munich, Germany.

Martine Vrijheid (M)

ISGlobal, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Thorkild I A Sørensen (TIA)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Department of Public Health, Section of Epidemiology, and The Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.

Rae-Chi Huang (RC)

Telethon Kids Institute, University of Western Australia, Perth, Australia.

Syed Hasan Arshad (SH)

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.

Wenche Nystad (W)

Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway.

Erik Melén (E)

Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.

Gerard H Koppelman (GH)

University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, Groningen, The Netherlands.
University Medical Center Groningen GRIAC Research Institute, University of Groningen, Groningen, the Netherlands.

Stephanie J London (SJ)

Department of Health and Human Services, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.

Nina Holland (N)

Children's Environmental Health Laboratory, Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.

Mariona Bustamante (M)

ISGlobal, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Susan K Murphy (SK)

Department of Obstetrics and Gynecology, Duke University Medical Center, Raleigh, NC, USA.

Marie-France Hivert (MF)

Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Universite de Sherbrooke, Sherbrooke, QC, Canada.

Andrea Baccarelli (A)

Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA.

Caroline L Relton (CL)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Harold Snieder (H)

University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.

Vincent W V Jaddoe (VWV)

The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Room Na-2918, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, the Netherlands.
Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Janine F Felix (JF)

The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Room Na-2918, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, the Netherlands. j.felix@erasmusmc.nl.
Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. j.felix@erasmusmc.nl.

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