Letter | Published:

A genome-wide association meta-analysis identifies new childhood obesity loci

Nature Genetics volume 44, pages 526531 (2012) | Download Citation

Abstract

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10−6 in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10−9; odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10−9; OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI1.

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Acknowledgements

Avon Longitudinal Study of Parents and Children (ALSPAC): The authors are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The authors would also like to acknowledge 23andMe for our genotyping collaboration. The UK MRC (74882), the Wellcome Trust (076467) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, and J.P.B. and S.F.A.G. will serve as guarantors for the content.

Northern Finnish Birth Cohort Studies 1966 (NFBC1966) and 1986 (NFBC1986): The authors thank P. Rantakallio (launch of NFBC1966 and NBC1986) and O. Tornwall and M. Jussila (DNA biobanking). The authors would like to acknowledge the contribution of the late Academian of Science Leena Peltonen. B.V. was supported by the Economic Social Research Council (ESRC; ES/H016058/1). J.B. is supported by a Wellcome Trust fellowship grant (WT088431MA). NFBC1966 and NFBC1986 received financial support from the Academy of Finland (104781, 120315, 129269, 1114194, the Center of Excellence in Complex Disease Genetics and SALVE), the University Hospital Oulu, the Biocenter Oulu, the University of Oulu (75617), the European Commission (EURO-BLCS; Framework 5 award; QLG1-CT-2000-01643), the US National Heart, Lung, and Blood Institute (NHLBI; 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01)), the US National Institutes of Health (NIH) and National Institute of Mental Health (NIMH; 5R01MH63706:02), the European Network for Genetic and Genomic Epidemiology (ENGAGE) project and grant agreement HEALTH-F4-2007-201413, the UK MRC (G0500539, G0600705 and PrevMetSyn/SALVE) and the Wellcome Trust (UK; GR069224). DNA extraction, sample quality control, biobank upkeep and aliquotting were performed at the National Public Health Institute at Biomedicum Helsinki (Finland) and were supported financially by the Academy of Finland and Biocentrum Helsinki.

British 1958 Birth Cohort (B58C): S. Ring, W. McArdle and J. Johnson are thanked for help with data linkage. E.H. holds the UK Department of Health Public Health Career Scientist Award. Analyses were funded by the British Heart Foundation (PG/09/023) and as part of the Public Health Research Consortium (supported by the UK Department of Health Policy Research Programme). C.M.L. is a Wellcome Trust Research Career Development Fellow (086596/Z/08/Z). R.M. was funded by grants from the European Commission Framework Programme 7 (FP7; 201413 and 245536), the Estonian government (SF0180142s08) and the European Union (EU) through the European Regional Development Fund (ERDF) and within the framework of the Centre of Excellence in Genomics and the University of Tartu (SP1GVARENG). The views expressed in this publication are those of the authors and not necessarily those of the UK Department of Health. Information about the wider program of the PHRC is available (see URLs). Collection of DNA in the 1958 Birth Cohort was funded by the UK MRC (G0000934) and the Wellcome Trust (068545/Z/02). This research used resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the US National Institute of Allergy and Infectious Diseases, the US National Human Genome Research Institute, the US National Institute of Child Health and Human Development and the Juvenile Diabetes Research Foundation International (JDRF) and supported by the NIDDK (U01 DK062418). This study makes use of data generated by the Wellcome Trust Case Control Consortium 2. A full list of investigators who contributed to generation of the data is available from the Wellcome Trust Case Control Consortium website. Funding for the project was provided by the Wellcome Trust (083948). Work was undertaken at Great Ormond Street Hospital and the Institute of Child Health at University College London, which received some funding from the UK Department of Health's NIHR (Biomedical Research Centres funding). The UK MRC provides funds for the MRC Centre of Epidemiology for Child Health.

French Young Study (FRENCH YOUNG): The authors thank the subjects and families who participated in this study. This work was supported by grants from the Agence Nationale de la Recherche, the Conseil Régional Nord-Pas de Calais as part of Fonds Européen de Développement Economique et Regional, Genome Quebec as part of Genome Canada and the UK MRC.

Lifestyle—Immune System—Allergy Study and German Infant Study on the Influence of Nutrition Intervention (LISA+GINI): The LISAplus study was funded by Helmholtz Zentrum München. The GINIplus study was funded by Helmholtz Zentrum München and by a grant from the German Federal Ministry for Education, Science, Research and Technology 292 (01 EE 9401-4). In addition, both studies were partly supported by the Competence Network Obesity, which receives funding from the German Federal Ministry of Education and Research (FKZ; 01GI0826) and the Munich Center of Health Sciences (MC Health) as part of the Ludwig-Maximilians University Munich (LMU) initiative.

Western Australian Pregnancy Cohort (RAINE) Study: The authors are grateful to the participants of the Raine Study and their families and to the Raine Study research staff for cohort coordination and data collection. The authors gratefully acknowledge the National Health and Medical Research Council of Australia for its long-term contribution to funding the study over the last 20 years and also acknowledge the following institutions for providing funding for the Core Management of the Raine Study: The University of Western Australia (UWA), the Raine Medical Research Foundation, the UWA Faculty of Medicine, Dentistry and Health Sciences, The Telethon Institute for Child Health Research, Curtin University and the Women and Infants Research Foundation. The authors gratefully acknowledge the assistance of the Western Australian DNA Bank (National Health and Medical Research Council of Australia National Enabling Facility). The authors also acknowledge the support of the National Health and Medical Research Council of Australia (403981 and 003209) and the Canadian Institutes of Health Research (MOP-82893).

Children's Hospital of Philadelphia (CHOP): The authors thank the network of primary care clinicians and the patients and families for their contribution to this project and to clinical research facilitated by the Pediatric Research Consortium (PeRC) at The Children's Hospital of Philadelphia. R. Chiavacci, E. Dabaghyan, H. Thomas, K. Harden, A. Hill, K. Fain, C. Johnson-Honesty, C. Drummond, S. Harrison, S. Wildrick, C. Kim, E. Frackelton, G. Otieno, K. Thomas, C. Hou, K. Thomas and M.L. Garris provided expert assistance with genotyping and/or data collection and management. The authors would also like to thank S. Kristinsson, L.A. Hermannsson and A.K. Raförninnehf for extensive software design and contributions. This research was financially supported by an Institute Development Award from the Children's Hospital of Philadelphia, a Research Development Award from the Cotswold Foundation and by a grant from the US NIH (R01 HD056465).

Essen Obesity Study (ESSEN): The authors thank all the participants of this study. This work was supported by grants from the German Federal Ministry of Education and Research (BMBF: 01KU0903 and NGFN-Plus: 01GS0820 and 01GS0830) and the Deutsche Forschungsgemeinschaft (DFG; HE 1446/4-1).

Helsinki Birth Cohort Study (HBCS): The Helsinki Birth Cohort Study (HBCS/HBCS 1934-44) thanks D. Barker, C. Osmond, E. Kajantie and T. Forsen. Major financial support was received from the Academy of Finland (209072 and 129255) and the British Heart Foundation. DNA extraction, sample quality control, biobank upkeep and aliquotting were performed at the National Institute for Health and Welfare (Helsinki, Finland).

Cardiovascular Risk in Young Finns Study (YF): The expert technical assistance in statistical analyses of I. Lisinen is gratefully acknowledged. The Young Finns Study has been financially supported by the Academy of Finland (126925, 121584, 124282, 129378 (SALVE), 117787 (Gendi) and 41071 (Skidi)), the Social Insurance Institution of Finland (Kuopio), Tampere and Turku University Hospital Medical Funds (9M048 for TeLeht), the Juho Vainio Foundation, the Paavo Nurmi Foundation, the Finnish Foundation of Cardiovascular Research, the Finnish Cultural Foundation, the Tampere Tuberculosis Foundation and the Emil Aaltonen Foundation.

Copenhagen Study on Asthma in Childhood (COPSAC): The authors thank all the families participating in the COPSAC cohort for their effort and commitment. The authors also thank the COPSAC study team. COPSAC is funded by private and public research funds, all of which are listed on the COPSAC website (see URLs). The Lundbeck Foundation, the Pharmacy Foundation of 1991, the Augustinus Foundation, the Danish MRC and The Danish Pediatric Asthma Centre provided core support for COPSAC. The funding agencies did not have any role in study design, data collection and analysis, the decision to publish or preparation of the manuscript.

Control Male–Genetics of Overweight Young Adults (CM-GOYA) study: This study was conducted as part of the activities of the Danish Obesity Research Centre (DanORC; see URLs) and the MRC Centre for Causal Analyses in Translational Epidemiology (UK MRC Causal Analyses in Translational Epidemiology (CAITE)).

Generation R Study (GENERATIONR): The authors gratefully acknowledge the contributions of the children and their parents, the general practitioners, the hospitals and the midwives and pharmacies in Rotterdam. The authors would like to thank K. Estrada, T.A. Knoch, A. Abuseiris, L.V. de Zeeuw and R. de Graaf for their help in creating GRIMP and BigGRID, MediGRID and Services@MediGRID/D-Grid (funded by the German Bundesministerium fuer Forschung und Technology; 01-AK-803-A-H and 01-IG-07015-G) for access to their grid computing resources. The authors thank M. Jhamai, M. Ganesh, P. Arp, M. Verkerk, L. Herrera and M. Peters for their help in creating, managing and performing quality control for the GWAS database. Also, the authors thank K. Estrada and C. Medina-Gomez for their support in the creation and analysis of imputed data. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and the Faculty of Social Sciences of Erasmus University Rotterdam, the Municipal Health Service, Rotterdam area, the Rotterdam Homecare Foundation and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC; Rotterdam). The generation and management of GWAS genotype data for the Generation R Study were performed at the Genetic Laboratory of the Department of Internal Medicine at Erasmus Medical Center. The Generation R Study is made possible by financial support from the Erasmus Medical Center (Rotterdam), the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development (ZonMw; 21000074). V.J. received grants from the Netherlands Organization for Health Research and Development (90700303 and 916.10159). Additional support was provided to H.R.T. by a grant from the Dutch Kidney Foundation (C08.2251).

Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study: The HELENA Study received funding from the EU Sixth Research and Technological Development (RTD) Framework Program (FOOD-CT-2005-007034). This work was also supported by the Conseil Régional du Nord-Pas de Calais and by the ERDF in the framework of the Contrat de Projet Etat-Région (CPER) Cardio-diabète (09220016).

Young Hearts Project: The Young Hearts Project has received support from the British Heart Foundation (PG/1996183/9569), the Wellcome Trust (052515/2/97/2) and the Department of Health and Social Services in Northern Ireland.

German Infant Study on the influence of Nutrition Intervention (GINI): GINI Munich: The study team wishes to acknowledge Helmholtz Zentrum München, the German Research Center for Environmental Health, the Institute of Epidemiology, Munich (J. Heinrich, H.E. Wichmann, S. Sausenthaler, C.-M. Chen, E. Thiering, C. Tiesler, M. Standl, M. Schnappinger and P. Rzehak), the Department of Pediatrics at Marien Hospital, Wesel (D. Berdel, A. von Berg, C. Beckmann and I. Groß), the Department of Pediatrics at Ludwig-Maximilians University, Munich (S. Koletzko, D. Reinhard and S. Krauss-Etschmann), the Department of Pediatrics at the Technical University, Munich (C.P. Bauer, I. Brockow, A. Grübl and U. Hoffmann), the Institut für Umweltmedizinische Forschung (IUF) at Heinrich-Heine-University, Düsseldorf (U. Krämer, E. Link and C. Cramer) and the Centre for Allergy and Environment at the Technical University, Munich (H. Behrendt).

Children's Health Study (CHS): The authors are indebted to the school principals, teachers, students and parents in each of the 12 study communities for their cooperation and especially thank the members of the health testing field team for their efforts. This work was supported by the Southern California Environmental Health Sciences Center (5P30ES007048) funded by the US National Institute of Environmental Health Sciences (NIEHS), the Children's Environmental Health Center (5P01ES009581, R826708-01 and RD831861-01) funded by the US NIEHS and the Environmental Protection Agency, the US NIEHS (5P01ES011627, 5R01ES014447, 5R01ES014708, 5R01ES016535 and 5R03ES014046), the US NHLBI (5R01HL061768, 5R01HL076647, 5R01HL087680, 1RC2HL101543 and 1RC2HL101651), the Environmental Protection Agency (R831845) and the Hastings Foundation.

Severe Childhood Onset Obesity Project United Kingdom (SCOOP-UK): The authors acknowledge the support of the Wellcome Trust (077016/Z/05/Z), the UK MRC and the NIHR Cambridge Biomedical Research Centre.

INfancia y Medio Ambiente (Environment and Childhood) Project (INMA): The authors are grateful to S. Fochs, A. Sànchez, M. López, N. Pey, M. Ferrer, A. Quiles, S. Pérez, G. León, E. Romero, M. Andreu, N. Galiana, M.D. Climent and A. Cases for their assistance in contacting the families and administering the questionnaires. The authors would particularly like to thank all the participants for their generous collaboration. A full roster of investigators at the INMA Project can be found at the project's website (see URLs). This study was funded by grants from the Instituto de Salud Carlos III (CB06/02/0041, G03/176, FIS PI041436, PI081151, PI041705, PS09/00432, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314 and 09/02647), the Spanish Ministry of Science and Innovation (SAF2008-00357), the European Commission (the ENGAGE Project and HEALTH-F4-2007-201413), the Fundació La Marató de TV3, the Generalitat de Catalunya (CIRIT 1999SGR 00241), the Conselleria de Sanitat Generalitat Valenciana and the Fundación Roger Torné. Part of the DNA extraction and genotyping was performed at the Spanish National Genotyping Centre (CEGEN-Barcelona).

Project Viva (VIVA): The authors thank the staff and participants of Project Viva and S. Rifas-Shiman for expert statistical programming. This work was supported by a grant from the US NIH (R01 DK075787).

Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study: The PIAMA birth cohort study is a collaboration of the Institute for Risk Assessment Sciences at University Utrecht (B. Brunekreef), the Centre for Prevention and Health Services Research, the National Institute for Public Health and the Environment, Bilthoven (A.H. Wijga and H.A. Smit), The Department of Pediatrics in the Division of Respiratory Medicine at Erasmus Medical Center–Sophia's Children Hospital, Rotterdam (J.C. de Jongste), the Departments of Epidemiology (M. Kerkhof), Pulmonology (D.S. Postma) and Pediatric Pulmonology and Pediatric Allergology (G.H. Koppelman) of the GRIAC Research Institute, the University Medical Center Groningen and the University of Groningen and the Department of Immunopathology at Sanquin Research, Amsterdam (R.C. Aalberse). The study team gratefully acknowledges the participants in the PIAMA birth cohort study and all coworkers who helped in conducting the medical examinations, field work and data management. The PIAMA study was funded by grants from the Dutch Asthma Foundation (3.4.01.26, 3.2.06.022, 3.4.09.081 and 3.2.10.085CO), the ZON-MW Netherlands Organization for Health Research and Development (912-03-031), the Stichting Astmabestrijding, the Ministry of the Environment and ZON-MW Biobanking and Biomolecular Research Infrastructure (BBMRI)-NL.

Author information

Author notes

    • Jonathan P Bradfield
    •  & H Rob Taal

    These authors contributed equally to this work.

Affiliations

  1. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    • Jonathan P Bradfield
    • , Patrick M A Sleiman
    • , Hakon Hakonarson
    •  & Struan F A Grant
  2. The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.

    • H Rob Taal
    • , Dennis O Mook-Kanamori
    • , Albert Hofman
    • , Ralf J P van der Valk
    • , Johan C de Jongste
    •  & Vincent W V Jaddoe
  3. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

    • H Rob Taal
    • , Dennis O Mook-Kanamori
    • , Albert Hofman
    • , Fernando Rivadeneira
    • , André G Uitterlinden
    • , Cornelia M van Duijn
    •  & Vincent W V Jaddoe
  4. Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.

    • H Rob Taal
    • , Dennis O Mook-Kanamori
    •  & Vincent W V Jaddoe
  5. The Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK.

    • Nicholas J Timpson
    • , David M Evans
    • , Beate St Pourcain
    • , John P Kemp
    •  & George Davey Smith
  6. Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany.

    • André Scherag
  7. Centre National de la Recherche Scientifique (CNRS) 8199, Université Lille Nord de France, Pasteur Institute, Lille, France.

    • Cecile Lecoeur
    • , Philippe Froguel
    •  & David Meyre
  8. School of Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.

    • Nicole M Warrington
    •  & Craig E Pennell
  9. Centre for Paediatric Epidemiology and Biostatistics, MRC Centre of Epidemiology for Child Health, University College London Institute of Child Health, London, UK.

    • Elina Hypponen
    • , Karani S Vimaleswaran
    • , Diane J Berry
    •  & Chris Power
  10. Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark.

    • Claus Holst
    •  & Thorkild I A Sørensen
  11. Department of Epidemiology and Biostatistics, MRC–Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.

    • Beatriz Valcarcel
    • , Paul Elliott
    • , Shikta Das
    •  & Marjo-Riitta Jarvelin
  12. Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute of Epidemiology I, Neuherberg, Germany.

    • Elisabeth Thiering
    •  & Joachim Heinrich
  13. Division of Genetics, Children's Hospital, Boston, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  14. Division of Endocrinology, Children's Hospital, Boston, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  15. Program in Genomics, Children's Hospital, Boston, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  16. Metabolism Program, Broad Institute, Cambridge, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  17. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  18. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • Rany M Salem
    • , Aarno Palotie
    •  & Joel N Hirschhorn
  19. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Fredrick R Schumacher
    • , W James Gauderman
    • , Mohamed T Hassanein
    •  & Frank D Gilliland
  20. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

    • Diana L Cousminer
    • , Aarno Palotie
    •  & Elisabeth Widen
  21. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    • Patrick M A Sleiman
    • , Jianhua Zhao
    • , Hakon Hakonarson
    •  & Struan F A Grant
  22. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Patrick M A Sleiman
    • , Hakon Hakonarson
    •  & Struan F A Grant
  23. Department of Child and Adolescent Psychiatry and Behavioral Sciences, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    • Robert I Berkowitz
  24. Center for Weight and Eating Disorders, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Robert I Berkowitz
  25. Institute of Medical Biometry and Epidemiology, Philipps–University of Marburg, Marburg, Germany.

    • Ivonne Jarick
  26. Department of Physiology and Biophysics, Weill Cornell Medical College–Qatar, Doha, Qatar.

    • Dennis O Mook-Kanamori
  27. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Fernando Rivadeneira
    •  & André G Uitterlinden
  28. Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC) Research Institute, University of Groningen, Groningen, The Netherlands.

    • Ralf J P van der Valk
  29. Division of Respiratory Medicine, Department of Pediatrics, Erasmus University Medical Center–Sophia Children's Hospital, Rotterdam, The Netherlands.

    • Ralf J P van der Valk
    •  & Johan C de Jongste
  30. Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, GRIAC Research Institute, University of Groningen, Groningen, The Netherlands.

    • Dirkje S Postma
  31. Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

    • Dorret I Boomsma
  32. Genetic and Genomic Epidemiology Unit, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Cecilia M Lindgren
    •  & Reedik Mägi
  33. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Reedik Mägi
  34. Institute for Sport and Health, University College Dublin, Dublin, Ireland.

    • Colin A G Boreham
  35. Centre for Public Health, Institute of Clinical Science B, Queen's University Belfast, Belfast, UK.

    • Charlotte E Neville
  36. Growth, Exercise, Nutrition and Development (GENUD) Research Group, Universidad de Zaragoza, Zaragoza, Spain.

    • Luis A Moreno
  37. School of Health Sciences (EUCS), Universidad de Zaragoza, Zaragoza, Spain.

    • Luis A Moreno
  38. Department of Lifecourse and Services, National Institute for Health and Welfare, Oulu, Finland.

    • Anneli Pouta
    •  & Marjo-Riitta Jarvelin
  39. Institute of Clinical Medicine/Obstetrics and Gynecology, University of Oulu, Oulu, Finland.

    • Anna-Liisa Hartikainen
  40. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Mingyao Li
  41. Department of Clinical Physiology, Turku University Hospital and University of Turku, Turku, Finland.

    • Olli Raitakari
  42. Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Tampere, Finland.

    • Terho Lehtimäki
  43. National Institute for Health and Welfare, Helsinki, Finland.

    • Johan G Eriksson
  44. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.

    • Johan G Eriksson
  45. Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.

    • Johan G Eriksson
  46. Folkhälsan Research Center, Helsinki, Finland.

    • Johan G Eriksson
  47. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Aarno Palotie
    • , Panos Deloukas
    • , Eleanor Wheeler
    •  & Inês Barroso
  48. Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.

    • Aarno Palotie
  49. Institut National de la Santé et la Recherche Médicale (INSERM), U744, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.

    • Jean Dallongeville
    •  & Aline Meirhaeghe
  50. School of Social and Community Medicine, University of Bristol, Bristol, UK.

    • George McMahon
    •  & Susan M Ring
  51. Section of Integrative Medicine, Imperial College London, London, UK.

    • Jessica L Buxton
    •  & Alexandra I F Blakemore
  52. Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.

    • Mariona Bustamante
    •  & Mònica Guxens
  53. Hospital del Mar Research Institute (IMIM), Barcelona, Spain.

    • Mariona Bustamante
    •  & Mònica Guxens
  54. Consorcio de Investigación Biomédica en Red (CIBER) Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain.

    • Mariona Bustamante
    •  & Mònica Guxens
  55. Genes and Disease Program, Center for Genomic Regulation (CRG) and Pompeu Fabra University (UPF), Barcelona, Spain.

    • Mariona Bustamante
  56. Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.

    • Matthew W Gillman
  57. Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen and Copenhagen University Hospital, Gentofte, Denmark.

    • Eskil Kreiner-Møller
    •  & Hans Bisgaard
  58. University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Inês Barroso
    • , Stephen O'Rahilly
    •  & I Sadaf Farooqi
  59. National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Inês Barroso
    • , Stephen O'Rahilly
    •  & I Sadaf Farooqi
  60. Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics, University of Copenhagen, Copenhagen, Denmark.

    • Thorkild I A Sørensen
  61. Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

    • Lyle J Palmer
  62. Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada.

    • Lyle J Palmer
  63. Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany.

    • Anke Hinney
    •  & Johannes Hebebrand
  64. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

    • Mark I McCarthy
  65. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Mark I McCarthy
  66. Oxford NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, UK.

    • Mark I McCarthy
  67. Department of Genomics of Common Disease, Imperial College London, London, UK.

    • Philippe Froguel
  68. Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.

    • David Meyre
  69. Institute of Health Sciences, University of Oulu, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  70. Biocenter Oulu, University of Oulu, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  71. Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Hakon Hakonarson
    •  & Struan F A Grant

Consortia

  1. the Early Growth Genetics (EGG) Consortium

    A full list of members is provided in the Supplementary Note.

Authors

    Contributions

    Project design was carried out by J.P.B., H.R.T., N.J.T., A.S., N.M.W., E.H., C.H., R.M.S., F.R.S., D.L.C., J.Z., R.I.B., R.J.P.v.d.V., J.C.d.J., D.I.B., W.J.G., L.A.M., M.L., H.B., F.D.G., J.H., I.B., S.O., A.M., T.I.A.S., C.P., L.J.P., A.H., E. Widen, I.S.F., M.I.M., P.F., D.M., J. Hebebrand, M.-R.J., V.W.V.J., G.D.S., H.H. and S.F.A.G. Sample collection and phenotyping was performed by H.R.T., R.M.S., R.I.B., C.E.P., A. Hofman, F.R., A.G.U., C.M.v.D., J.C.d.J., D.S.P., W.J.G., R.M., C.A.G.B., C.E.N., L.A.M., A. Pouta, A.-L.H., O.R., T.L., J.G.E., A. Palotie, J.D., P.D., G.M., S.M.R., J.P.K., J.L.B., A.I.F.B., M.B., M.G., J.N.H., M.W.G., H.B., F.D.G., J.H., I.B., S.O., A.M., T.I.A.S., C.P., L.J.P., A.H., I.S.F., M.I.M., P.F., D.M., J. Hebebrand, M.-R.J., V.W.V.J., G.D.S., H.H. and S.F.A.G. Genotyping was performed by R.M.S., C.E.P., D.M.E., D.J.B., A. Hofman, F.R., A.G.U., C.M.v.D., R.J.P.v.d.V., J.C.d.J., D.S.P., W.J.G., R.M., A. Pouta, A.-L.H., O.R., T.L., J.G.E., A. Palotie, J.D., P.D., G.M., S.M.R., J.P.K., J.L.B., A.I.F.B., M.B., J.N.H., M.W.G., H.B., J.H., I.B., S.O., A.M., T.I.A.S., C.P., L.J.P., A.H., E. Widen, I.S.F., M.I.M., P.F., D.M., J. Hebebrand, M.-R.J., V.W.V.J., G.D.S., H.H. and S.F.A.G. Statistical analysis was performed by J.P.B., H.R.T., N.J.T., A.S., C.L., N.M.W., E.H., C.H., B.V., E.T., R.M.S., F.R.S., D.L.C., P.M.A.S., J.Z., K.S.V., I.J., D.M.E., B.S.P., D.J.B., D.O.M.-K., F.R., R.J.P.v.d.V., J.C.d.J., D.S.P., W.J.G., M.T.H., C.M.L., R.M., P.E., A. Pouta, M.L., O.R., T.L., J.G.E., S.D., A.I.F.B., M.B., E.K.-M., E.W., A.M., A.H., E. Widen., I.S.F., D.M., M.-R.J., V.W.V.J., H.H. and S.F.A.G. The manuscript was written by J.P.B., H.R.T., N.J.T., A.S., J.Z., T.I.A.S., A.H., M.I.M., D.M., M.-R.J., V.W.V.J., H.H. and S.F.A.G.

    Competing interests

    The author declare no competing financial interests.

    Corresponding author

    Correspondence to Struan F A Grant.

    Supplementary information

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      Supplementary Text and Figures

      Supplementary Note, Supplementary Tables 1–10 and Supplementary Figures 1 and 2

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    DOI

    https://doi.org/10.1038/ng.2247

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