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Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations

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Abstract

We analyzed genome-wide association data from 1,380 Europeans with early-onset and morbid adult obesity and 1,416 age-matched normal-weight controls. Thirty-eight markers showing strong association were further evaluated in 14,186 European subjects. In addition to FTO and MC4R, we detected significant association of obesity with three new risk loci in NPC1 (endosomal/lysosomal Niemann-Pick C1 gene, P = 2.9 × 10−7), near MAF (encoding the transcription factor c-MAF, P = 3.8 × 10−13) and near PTER (phosphotriesterase-related gene, P = 2.1 × 10−7).

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Acknowledgements

We 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 Regional Nord-Pas de Calais/Fonds européen de développement économique et régional,” Genome Quebec/Genome Canada and the Medical Research Council. The German cohorts and projects were supported by grants from the German Research Council (KFO152 “Atherobesity”). We thank F. Allegaert, M. Deweirder, R. Tauscher and A. Berthold for their technical support in DNA extraction and distribution. We thank P. Bougnères and C. Le Stunff for providing DNA samples of the “Saint Vincent de Paul” obese children cohort. Northern Finland Birth Cohort 1986 (NFBC1986) was supported by the European Commission; contract number QLG1-CT-2000-01643, Biocenter, University of Oulu, Finland and the Academy of Finland. We thank L. Peltonen for providing NFBC1986 DNA samples. We acknowledge the “Centre de Médecine Préventive (CMP) de Vandoeuvre les Nancy” where the STANISLAS cohort was recruited.

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Authors and Affiliations

  1. CNRS 8090-Institute of Biology, Pasteur Institute, Lille, 59000, France

    David Meyre, Jérôme Delplanque, Jean-Claude Chèvre, Cécile Lecoeur, Stéphane Lobbens, Sophie Gallina, Emmanuelle Durand, Vincent Vatin, Franck Degraeve, Christine Proença, Stefan Gaget, Christian Dina & Philippe Froguel

  2. University Hospital for Children & Adolescents, University of Leipzig, Leipzig, 04103, Germany

    Antje Körner & Wieland Kiess

  3. Interdisciplinary Centre for Clinical Research, University of Leipzig, Leipzig, 04103, Germany

    Peter Kovacs

  4. Institut Inter Régional pour la Santé, La Riche, 37521, France

    Jean Tichet

  5. Department of Endocrinology, Diabetology, Nutrition, Bichat-Claude Bernard University Hospital, Assistance Publique des Hôpitaux de Paris, 75018 Paris, France, and Institut National de la Santé et de la Recherche Médicale U695, Université Paris 7, Paris, 75007, France

    Michel Marre

  6. Department of Clinical Sciences/ Obstetrics and Gynecology, University of Oulu, University of Oulu, Oulu, 90014, Finland

    Anna-Liisa Hartikainen

  7. Klinik Lindberg, 8400 Winterthur, and University of Berne, Berne, 3012, Switzerland

    Fritz Horber & Natascha Potoczna

  8. Unité Mixte de Recherche U557 Institut National de la Santé et de la Recherche Médicale, U1125 Institut National de la Recherche Agronomique, Conservatoire National des arts et Métiers, Université Paris 13, Centre de Recherches en Nutrition Humaine Ile de France, Bobigny, F-93017, France

    Serge Hercberg

  9. Institut National de la Santé et de la Recherche Médicale, U690, Paris, FR-75019, France

    Claire Levy-Marchal

  10. Université Paris Diderot, Paris, cedex 13, FR-75205, France

    Claire Levy-Marchal

  11. Institut National de la Santé et de la Recherche Médicale U859, Centre Hospitalier Régional Universitaire de Lille, Lille North of France University, Lille, 59000, France

    François Pattou

  12. Institut National de la Santé et de la Recherche Médicale U780, Villejuif, F-94807; University Paris-Sud, Orsay, F-91405, France

    Barbara Heude & Beverley Balkau

  13. Institut National de la Santé et de la Recherche Médicale U563, Children's Hospital, Centre Hospitalier Universitaire, Toulouse, 31000, France

    Maithé Tauber

  14. Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, OX3 7LJ, UK

    Mark I McCarthy

  15. Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 Oxford, UK

    Mark I McCarthy

  16. Oxford National Institute for Health Research Biomedical Research Centre, OX3 Oxford, UK

    Mark I McCarthy

  17. Section of Genomic Medicine, Hammersmith Hospital, Imperial College London, London, W12 0HS, UK

    Alexandra I F Blakemore, Julian Asher, Andrew Walley & Philippe Froguel

  18. McGill University and Genome Quebec Innovation Centre, Montreal, H3A 1A, Canada

    Alexandre Montpetit, Constantin Polychronakos & Rob Sladek

  19. Pediatric Endocrine Unit, Jeanne de Flandre Hospital, Lille, 59000, France

    Jacques Weill

  20. Department of Epidemiology and Public Health, Imperial College London, London, WC1E 6BT, UK

    Lachlan J M Coin, Paul Elliott, Marjo-Riitta Järvelin & David Balding

  21. Department of Child and Adolescent Health, Institute of Health Sciences, University of Oulu, National Public Health Institute, Biocenter Oulu, University of Oulu, Oulu, 90014, Finland

    Marjo-Riitta Järvelin

  22. Institut National de la Santé et de la Recherche Médicale “Cardiovascular Genetics” team, Centre D'investigation Clinique, Nancy, 54000, France

    Sophie Visvikis-Siest

Authors
  1. David Meyre
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  2. Jérôme Delplanque
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  3. Jean-Claude Chèvre
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  4. Cécile Lecoeur
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  5. Stéphane Lobbens
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  6. Sophie Gallina
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  7. Emmanuelle Durand
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  8. Vincent Vatin
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  9. Franck Degraeve
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  10. Christine Proença
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  11. Stefan Gaget
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  12. Antje Körner
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  13. Peter Kovacs
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  14. Wieland Kiess
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  15. Jean Tichet
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  16. Michel Marre
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  17. Anna-Liisa Hartikainen
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  18. Fritz Horber
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  19. Natascha Potoczna
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  20. Serge Hercberg
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  21. Claire Levy-Marchal
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  22. François Pattou
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  23. Barbara Heude
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  24. Maithé Tauber
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  25. Mark I McCarthy
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  26. Alexandra I F Blakemore
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  27. Alexandre Montpetit
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  28. Constantin Polychronakos
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  29. Jacques Weill
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  30. Lachlan J M Coin
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  31. Julian Asher
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  32. Paul Elliott
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  33. Marjo-Riitta Järvelin
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  34. Sophie Visvikis-Siest
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  35. Beverley Balkau
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  36. Rob Sladek
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  37. David Balding
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  38. Andrew Walley
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  39. Christian Dina
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  40. Philippe Froguel
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Contributions

Writing team: D.M., P.F., J.-C.C., A.I.F.B., M.I.M., A.W., C.D., R.S.; all others reviewed and approved the manuscript. Project management: D.M., J.D., A.W., C.D., P.F. Genome-wide association sampling and genotyping: D.M., J.D., S.L., E.D., J.T., M.M., M.T., S.V.-S., R.S., B.H., A.M., C.P., B.B. Confirmation study sampling and genotyping: D.M., J.D., E.D., V.V., A.K., P.K., W.K., J.T., M.M., A.L.H., P.E., F.H., N.P., S.H., C.L-.M., F.P., B.H., J.W., M.-R.J., B.B. Statistical analysis and informatics: D.M., C.L., S.G., F.D., C.P., S.G., L.J.M.C., J.A., D.B., C.D. Candidate gene analysis: J.C.C., D.M., S.G., F.D., S.G.

Corresponding author

Correspondence to Philippe Froguel.

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Supplementary Figures 1 and 2, Supplementary Tables 1–4 and Supplementary Methods (PDF 1279 kb)

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Meyre, D., Delplanque, J., Chèvre, JC. et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 41, 157–159 (2009). https://doi.org/10.1038/ng.301

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  • DOI: https://doi.org/10.1038/ng.301

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